The incorporation of acetylated LAP-TGF-ß1 proteins into exosomes promotes TNBC cell dissemination in lung micro-metastasis.

Triple-negative breast cancer (TNBC) stands as the breast cancer subtype with the highest recurrence and mortality rates, with the lungs being the common site of metastasis. The pulmonary microenvironment plays a pivotal role in the colonization of disseminated tumor cells. Herein, this study highlights the crucial role of exosomal LAP-TGF-ß1, the principal form of exosomal TGF-ß1, in reshaping the pulmonary vascular niche, thereby facilitating TNBC lung metastasis. Although various strategies have been developed to block TGF-ß signaling and have advanced clinically, their significant side effects have limited their therapeutic application. This study demonstrates that in lung metastatic sites, LAP-TGF-ß1 within exosomes can remarkably reconfigure the pulmonary vascular niche at lower doses, bolstering the extravasation and colonization of TNBC cells in the lungs. Mechanistically, under the aegis of the acetyltransferase TIP60, a non-canonical KFERQ-like sequence in LAP-TGF-ß1 undergoes acetylation at the K304 site, promoting its interaction with HSP90A and subsequent transport into exosomes. Concurrent inhibition of both HSP90A and TIP60 significantly diminishes the exosomal burden of LAP-TGF-ß1, presenting a promising therapeutic avenue for TNBC lung metastasis. This study not only offers fresh insights into the molecular underpinnings of TNBC lung metastasis but also lays a foundation for innovative therapeutic strategies.

A Reconfigurable DNA Framework Nanotube-Assisted Antiangiogenic Therapy.

A major limitation of tumor antiangiogenic therapy is the pronounced off-target effect, which can lead to unavoidable injury in multiple organs. Ensuring sufficient delivery and controlled release of these antiangiogenic agents at tumor sites is crucial for realizing their clinical application. Here, we develop a smart DNA-based nanodrug, termed Endo-rDFN, by precisely assembling the antiangiogenic agent, endostar (Endo), into a reconfigurable DNA framework nanotube (rDFN) that could recognize tumor-overexpressed nucleolin to achieve the targeted delivery and controllable release of Endo. Endo-rDFN can not only effectively enhance the tumor-targeting capability of Endo and maintain its efficient accumulation in tumor tissues but also achieve on-demand release of Endo at tumor sites via the specific DNA aptamer for tumor-overexpressed nucleolin, named AS1411. We also found that Endo-rDFN exhibited significant inhibition of angiogenesis and tumor growth, while also providing effective protection against multiorgan injury (heart, liver, spleen, kidney, lung, etc.) to some extent, without compromising the function of these organs. Our study demonstrates that rDFN represents a promising vector for reducing antiangiogenic therapy-induced multiorgan injury, highlighting its potential for promoting the clinical application of antiangiogenic agents.

A novel method-based reinforcement learning with deep temporal difference network for flexible double shop scheduling problem.

This paper studies the flexible double shop scheduling problem (FDSSP) that considers simultaneously job shop and assembly shop. It brings about the problem of scheduling association of the related tasks. To this end, a reinforcement learning algorithm with a deep temporal difference network is proposed to minimize the makespan. Firstly, the FDSSP is defined as the mathematical model of the flexible job-shop scheduling problem joined to the assembly constraint level. It is translated into a Markov decision process that directly selects behavioral strategies according to historical machining state data. Secondly, the proposed ten generic state features are input into the deep neural network model to fit the state value function. Similarly, eight simple constructive heuristics are used as candidate actions for scheduling decisions. From the greedy mechanism, optimally combined actions of all machines are obtained for each decision step. Finally, a deep temporal difference reinforcement learning framework is established, and a large number of comparative experiments are designed to analyze the basic performance of this algorithm. The results showed that the proposed algorithm was better than most other methods, which contributed to solving the practical production problem of the manufacturing industry.

Diet and lifestyle behaviours simultaneously act on frailty: it is time to move the threshold of frailty prevention and control forward.

BACKGROUND: To analyse the association among the simultaneous effects of dietary intake, daily life behavioural factors, and frailty outcomes in older Chinese women, we predicted the probability of maintaining physical robustness under a combination of different variables. METHODS: The Fried frailty criterion was used to determine the three groups of "frailty", "pre-frailty", and "robust", and a national epidemiological survey was performed. The three-classification decision tree model was fitted, and the comprehensive performance of the model was evaluated to predict the probability of occurrence of different outcomes. RESULTS: Among the 1,044 participants, 15.9% were frailty and 50.29% were pre-frailty; the overall prevalence first increased and then decreased with age, reaching a peak at 70-74 years of age. Through univariate analysis, filtering, and embedded screening, eight significant variables were identified: staple food, spices, exercise (frequency, intensity, and time), work frequency, self-feeling, and family emotions. In the three-classification decision tree, the values of each evaluation index of Model 3 were relatively average; the accuracy, recall, specificity, precision, and F1 score range were between 75% and 84%, and the AUC was also greater than 0.800, indicating excellent performance and the best interpretability of the results. Model 3 takes exercise time as the root node and contains 6 variables and 10 types, suggesting the impact of the comprehensive effect of these variables on robust and non-robust populations (the predicted probability range is 6.67-93.33%). CONCLUSION: The combined effect of these factors (no exercise or less than 0.5 h of exercise per day, occasional exercise, exercise at low intensity, feeling more tired at work, and eating too many staple foods (> 450 g per day) are more detrimental to maintaining robustness.

Cross-kingdom RNA interference mediated by insect salivary microRNAs may suppress plant immunity.

Communication between insects and plants relies on the exchange of bioactive molecules that traverse the species interface. Although proteinic effectors have been extensively studied, our knowledge of other molecules involved in this process remains limited. In this study, we investigate the role of salivary microRNAs (miRNAs) from the rice planthopper Nilaparvata lugens in suppressing plant immunity. A total of three miRNAs were confirmed to be secreted into host plants during insect feeding. Notably, the sequence-conserved miR-7-5P is specifically expressed in the salivary glands of N. lugens and is secreted into saliva, distinguishing it significantly from homologues found in other insects. Silencing miR-7-5P negatively affects N. lugens feeding on rice plants, but not on artificial diets. The impaired feeding performance of miR-7-5P-silenced insects can be rescued by transgenic plants overexpressing miR-7-5P. Through target prediction and experimental testing, we demonstrate that miR-7-5P targets multiple plant genes, including the immune-associated bZIP transcription factor 43 (OsbZIP43). Infestation of rice plants by miR-7-5P-silenced insects leads to the increased expression of OsbZIP43, while the presence of miR-7-5P counteracts this upregulation effect. Furthermore, overexpressing OsbZIP43 confers plant resistance against insects which can be subverted by miR-7-5P. Our findings suggest a mechanism by which herbivorous insects have evolved salivary miRNAs to suppress plant immunity, expanding our understanding of cross-kingdom RNA interference between interacting organisms.

Comprehensive analysis of CYBB as a prognostic marker and therapeutic target in glioma: A bioinformatics approach.

Background: In the central nervous system, glioma is the most common malignant tumor, and patients have a poor prognosis. Identification of novel marker genes and establishment of prognostic models are important for early diagnosis and prognosis determination. Methods: Download glioma data from the CGGA and TCG databases. Application of bioinformatics to analyze the impact of CYBB on the clinicopathological characteristics, immunological features and prognosis of gliomas. Using single-cell sequencing data from 7 glioblastoma patients in the CGGA database, the role of CYBB in the tumor microenvironment was analyzed. In addition, a prognostic model was constructed based on CYBB high and low differentially expressed genes and mitochondrial genes. Results: The expression of CYBB is closely related to various clinical features, immune cell infiltration level, immune checkpoint and survival time of patients. A 10-gene prediction model was constructed based on the differentially expressed genes of low and high CYBB and mitochondria-related genes. Glioma patients with higher risk scores had significantly lower survival probabilities. Receiver operating characteristic curves and nomograms were plotted over time to show the predictive accuracy and predictive value of the 10-gene prognostic model. Conclusions: Our study shows that CYBB is strongly correlated with clinical characteristics features and prognosis of glioma patients, and can be used as a potential therapeutic target. Prognostic models based on CYBB and mitochondrial genes have good performance in predicting prognosis of glioma patients.

1D hollow tubular/2D nanosheet hybrid dimensional porous carbon prepared by one-step carbonization using natural minerals as templates for supercapacitors.

The reasonable construction of one-dimensional (1D)/two-dimensional (2D) hybrid dimensional porous carbon materials with complementary advantages and disadvantages is an important approach to addressing the structural and performance deficiencies of single carbon materials, while also significantly improving the electrochemical performance of super-capacitors. In this study, 1D hollow tubular/2D nanosheet hybrid dimensional porous carbon was synthesized through one-step carbonization using 1D fibrous brucite and 2D layered magnesium carbonate hydroxide as templates. By adjusting the feed ratio of 1D fibrous and 2D layered templates, the morphology, pore structure and specific surface area (SSA) of the prepared 1D hollow tubular/2D nanosheet hybrid dimensional porous carbon were controlled. The prepared hybrid dimensional porous carbons were characterized using scanning electron microscope (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and nitrogen adsorption-desorption. And their electrochemical performance was also studied by cyclic voltammograms (CV), galvanostatic charge/discharge (GCD) and electrochemical impedance spectroscopy (EIS). The results show that the use of templates with different dimensions significantly influences the morphology, pore structure, SSA and electrochemical performance of the synthesized hybrid dimensional porous carbon. The hybrid dimensional porous carbon (3F) exhibits a high specific capacitance and excellent cycling stability. 3F demonstrates the specific capacitance of 245.3 F g-1 at 1 A g-1. Furthermore, the capacity retention rate remains as high as 93.4% after 8000 cycles at 10 A g-1. This work reveals that hybrid dimensional porous carbon composed of 1D hollow carbon tubes and 2D carbon nanosheets has great potential for use in supercapacitor electrode materials.

The role of anger rumination as a mediator in the relationship between driver moral disengagement and driving angry.

Background: Road rage is a common phenomenon during driving, which not only affects the psychological health of drivers but also may increase the risk of traffic accidents. This article explores the impact of moral disengagement and anger rumination on road rage through two studies. Method: This research combined experimental studies with survey questionnaires. Study one used a driving simulator to investigate whether moral disengagement and anger rumination are psychological triggers of road rage in real-time driving, and whether there are differences in the main psychological triggers of road rage under different road scenarios. Building on the first study, study two employed a survey questionnaire to analyze the relationship between moral disengagement, anger rumination, and road rage. Participants in both studies were drivers with certain driving ages and experience. Data were processed and analyzed using descriptive statistics, factor analysis, reliability and validity tests, and multiple regression analysis. Results: The findings indicated: (1) There were significant differences in the anger induction rate across different road scenarios, χ2 = 35.73, p < 0.01, effect size = 0.29. Significant differences in average anger levels were observed in scenarios involving oncoming vehicles, lane-cutting, sudden stops by the vehicle ahead, pedestrians crossing the road, and traffic congestion (F = 20.41, p < 0.01, ηp2 = 0.36), with anger rumination playing a major role in the formation of road rage; (2) Moral disengagement significantly predicted road rage (ß = 0.25, t = 3.85, p < 0.01). The predictive effect of moral disengagement on anger rumination was significant (ß = 0.39, t = 6.17, p < 0.01), as was the predictive effect of anger rumination on road rage (ß = 0.43, t = 6.3, p < 0.01). The direct effect of moral disengagement on road rage included 0 in the bootstrap 95% confidence interval, while the mediating effect of anger rumination did not include 0 in the bootstrap 95% confidence interval, indicating that anger rumination fully mediated the relationship between moral disengagement and road rage.

Ion Transport in Polymer Electrolytes: Building New Bridges between Experiment and Molecular Simulation.

ConspectusPolymer electrolytes constitute a promising type of material for solid-state batteries. However, one of the bottlenecks for their practical implementation lies in the transport properties, often including restricted Li+ self-diffusion and conductivity and low cationic transference numbers. This calls for a molecular understanding of ion transport in polymer electrolytes in which molecular dynamics (MD) simulation can provide both new physical insights and quantitative predictions. Although efforts have been made in this area and qualitative pictures have emerged, direct and quantitative comparisons between experiment and simulation remain challenging because of the lack of a unified theoretical framework to connect them.In our work, we show that by computing the glass transition temperature (Tg) of the model system and using the normalized inverse temperature 1000/(T - Tg + 50), the Li+ self-diffusion coefficient can be compared quantitatively between MD simulations and experiments. This allows us to disentangle the effects of Tg and the polymer dielectric environment on ion conduction in polymer electrolytes, giving rise to the identification of an optimal solvating environment for fast ion conduction.Unlike Li+ self-diffusion coefficients and ionic conductivity, the transference number, which describes the fraction of current carried by Li+ ions, depends on the boundary conditions or the reference frame (RF). This creates a non-negligible gap when comparing experiment and simulation because the fluxes in the experimental measurements and in the linear response theory used in MD simulation are defined in different RFs. We show that by employing the Onsager theory of ion transport and applying a proper RF transformation, a much better agreement between experiment and simulation can be achieved for the PEO-LiTFSI system. This further allows us to derive the theoretical expression for the Bruce-Vincent transference number in terms of the Onsager coefficients and make a direct comparison to experiments. Since the Bruce-Vincent method is widely used to extract transference numbers from experimental data, this opens the door to calibrating MD simulations via reproducing the Bruce-Vincent transference number and using MD simulations to predict the true transference number.In addition, we also address several open questions here such as the time-scale effects on the ion-pairing phenomenon, the consistency check between different types of experiments, the need for more accurate force fields used in MD simulations, and the extension to multicomponent systems. Overall, this Account focuses on building new bridges between experiment and simulation for quantitative comparison, warnings of pitfalls when comparing apples and oranges, and clarifying misconceptions. From a physical chemistry point of view, it connects to concentrated solution theory and provides a unified theoretical framework that can maximize the power of MD simulations. Therefore, this Account will be useful for the electrochemical energy storage community at large and set examples of how to approach experiments from theory and simulation (and vice versa).

[Effectiveness analysis of revision surgery after total hip arthroplasty assisted by artificial intelligence preoperative planning system].

Objective: To explore the short-term effectiveness of hip revision surgery guided by artificial intelligence preoperative planning (AIHIP) system. Methods: The clinical data of 22 patients (23 hips) who were admitted between June 2019 and March 2023 and met the selection criteria were retrospectively analyzed. There were 12 males and 10 females with an average age of 69.7 years (range, 44-90 years). There were 19 hips in the first revision, 3 hips in the second revision, and 1 hip in the third revision. The causes of revision included 12 hips with prosthesis loosening, 4 hips with acetabular cup loosening, 3 hips with osteolysis, 2 hips with acetabular dislocation, 1 hip with postoperative infection, and 1 hip with prosthesis wear. There were 6 hips in stage ⅡA, 9 hips in stage ⅡB, 4 hips in stage ⅡC, 3 hips in stage ⅢA, and 1 hip in stage ⅢB according to Paprosky staging of acetabular bone defect. The replacement of prosthesis type, operation time, hospitalization stay, ground active condition, and postoperative infection, fracture, prosthesis loosening, and other adverse events were recorded. The function of the affected limb was evaluated by Harris score before operation, at 1 week and 6 months after operation, and the range of motion of the hip joint was compared before operation and at 6 months after operation. Results: The operation time was 85-510 minutes, with an average of 241.8 minutes; the hospitalization stay was 7-35 days, with an average of 15.2 days; the time of disassociation from the walker was 2-108 days, with an average of 42.2 days. All the 22 patients were followed up 8-53 months (mean, 21.7 months). No adverse events such as prosthesis loosening or infection occurred in the rest of the patients, except for postoperative hematoma of the thigh in 1 patient and dislocation of the hip in 1 hip. The matching degree of acetabular cup was completely matched in 22 hips and mismatched in 1 hip (+2), the matching rate was 95.65%. The matching degree of femoral stem was completely matched in 22 hips and generally matched in 1 hip (-1), and the matching rate was 100%. The Harris scores were 55.3±9.8 and 89.6±7.2 at 1 week and 6 months after operation, respectively, which significantly improved when compared with before operation (33.0±8.6, P<0.05), and further improved at 6 months after operation than at 1 week after operation ( P<0.05). The function of hip joint was evaluated by Harris score at 6 months after operation, and 21 hips were good and 2 hips were moderate, which could meet the needs of daily life. The range of motion of hip joint was (111.09±10.11)° at 6 months after operation, which was significantly different from (79.13±18.50)° before operation ( t=-7.269, P<0.001). Conclusion: AIHIP system can improve the accuracy of revision surgery, reduce the difficulty of surgery, and achieve good postoperative recovery and satisfactory short-term effectiveness.

Clot removAl with or without decompRessive craniectomy under ICP monitoring for supratentorial IntraCerebral Hemorrhage (CARICH): a randomized controlled trial.

BACKGROUND: Decompressive craniectomy, a surgery to remove part of the skull and open the dura mater, maybe an effective treatment for controlling intracranial hypertension. It remains great interest to elucidate whether decompressive craniectomy is beneficial to intracerebral hemorrhage patients who warrant clot removal to prevent intracranial hypertension. METHODS: The trial was a prospective, pragmatic, controlled trial involving adult patients with intracerebral hemorrhage who were undergoing removal of hematoma. Intracerebral hemorrhage patients were randomly assigned at a 1:1 ratioto undergo clot removal with or without decompressive craniectomy under the monitoring of intracranial pressure. The primary outcome was the proportion of unfavorable functional outcome (modified Rankin Scale 3-6) at 3 months. Secondary outcomes included the mortality at 3 months and the occurrence of re-operation. RESULTS: A total of 102 patients were assigned to the clot removal with decompressive craniectomy group and 102 to the clot removal group. Median hematoma volume was 54.0 mL (range 30-80 mL) and median preoperative Glasgow Coma Scale was 10 (range 5-15). At 3 months, 94 patients (92.2%) in clot removal with decompressive craniectomy group and 83 patients (81.4%) in the clot removal group had unfavorable functional outcome (P=0.023). Fourteen patients (13.7%) in the clot removal with decompressive craniectomy group died versus five patients (4.9%) in the clot removal group (P=0.030). The number of patients with re-operation was similar between the clot removal with decompressive craniectomy group and clot removal group (5.9% vs. 3.9%; P=0.517). Postoperative intracranial pressure values were not significantly different between two groups and the mean values were less than 20 mmHg. CONCLUSIONS: Clot removal without decompressive craniectomy decreased the rate of modified Rankin Scale score of 3-6 and mortality in patients with intracerebral hemorrhage, compared with clot removal with decompressive craniectomy.

Robust deep learning from incomplete annotation for accurate lung nodule detection.

Deep learning plays a significant role in the detection of pulmonary nodules in low-dose computed tomography (LDCT) scans, contributing to the diagnosis and treatment of lung cancer. Nevertheless, its effectiveness often relies on the availability of extensive, meticulously annotated dataset. In this paper, we explore the utilization of an incompletely annotated dataset for pulmonary nodules detection and introduce the FULFIL (Forecasting Uncompleted Labels For Inexpensive Lung nodule detection) algorithm as an innovative approach. By instructing annotators to label only the nodules they are most confident about, without requiring complete coverage, we can substantially reduce annotation costs. Nevertheless, this approach results in an incompletely annotated dataset, which presents challenges when training deep learning models. Within the FULFIL algorithm, we employ Graph Convolution Network (GCN) to discover the relationships between annotated and unannotated nodules for self-adaptively completing the annotation. Meanwhile, a teacher-student framework is employed for self-adaptive learning using the completed annotation dataset. Furthermore, we have designed a Dual-Views loss to leverage different data perspectives, aiding the model in acquiring robust features and enhancing generalization. We carried out experiments using the LUng Nodule Analysis (LUNA) dataset, achieving a sensitivity of 0.574 at a False positives per scan (FPs/scan) of 0.125 with only 10% instance-level annotations for nodules. This performance outperformed comparative methods by 7.00%. Experimental comparisons were conducted to evaluate the performance of our model and human experts on test dataset. The results demonstrate that our model can achieve a comparable level of performance to that of human experts. The comprehensive experimental results demonstrate that FULFIL can effectively leverage an incomplete pulmonary nodule dataset to develop a robust deep learning model, making it a promising tool for assisting in lung nodule detection.

Treating cancer through modulating exosomal protein loading and function: The prospects of natural products and traditional Chinese medicine.

Exosomes, small yet vital extracellular vesicles, play an integral role in intercellular communication. They transport critical components, such as proteins, lipid bilayers, DNA, RNA, and glycans, to target cells. These vesicles are crucial in modulating the extracellular matrix and orchestrating signal transduction processes. In oncology, exosomes are pivotal in tumor growth, metastasis, drug resistance, and immune modulation within the tumor microenvironment. Exosomal proteins, noted for their stability and specificity, have garnered widespread attention. This review delves into the mechanisms of exosomal protein loading and their impact on tumor development, with a focus on the regulatory effects of natural products and traditional Chinese medicine on exosomal protein loading and function. These insights not only offer new strategies and methodologies for cancer treatment but also provide scientific bases and directions for future clinical applications.

Effect of acupuncture timing on functional impairment at 6 months post-onset in patients with first-ever stroke: a prospective cohort study. / é’ˆåˆºæ—¶æœºå¯¹é¦–æ¬¡ä¸­é£Žæ‚£è€ å‘ç— åŽ6ä¸ªæœˆåŠŸèƒ½éšœç¢çš„å½±å“ï¼šå‰çž»æ€§é˜Ÿåˆ—ç ”ç©¶.

OBJECTIVES: To observe the effect of acupuncture intervention in the acute phase on functional impairment at 6 months post-onset in patients with first-ever stroke, and provide evidence for selecting optimal acupuncture timing in the real-world setting. METHODS: A total of 601 patients with first-ever stroke were divided into an acute intervention group (onset within 14 days, 256 cases) and a non-acute intervention group (onset between 15 and 90 days, 345 cases) based on whether they received acupuncture treatment in the acute phase. The assessments were conducted at baseline and 6 months post-onset, including modified Rankin scale (mRS) score, total number of acupuncture sessions, total number of combined therapies (moxibustion, cupping, tuina and rehabilitation treatment), recurrence, death events and disability. Logistic regression analysis was used to analyze the association between acupuncture timing and the risk of disability at 6 months post-onset. The mRS transition method was employed to assess the effect of acupuncture timing on functional improvement at 6 months post-onset. RESULTS: Without adjusting for confounding factors, compared with the non-acute intervention group, the patients in the acute intervention group had reduced risk of disability at 6 months post-onset (OR=0.434, 95%CI: 0.309-0.609, P=0.000). After adjusting for variables i.e. severity of illness, number of acupuncture sessions, and number of cupping sessions, compared with the non-acute intervention group, the patients in the acute intervention group had reduced risk of disability at 6 months post-onset (OR=0.588, 95%CI: 0.388-0.890, P=0.012). After adjusting for all confounding factors, including severity of illness, number of acupuncture sessions, number of cupping sessions, gender, smoking and drinking history, comorbidities, and diagnosis, compared with the non-acute intervention group, the patients in the acute intervention group continued to have a reduced risk of disability at 6 months post-onset (OR=0.629, 95%CI: 0.408-0.971, P=0.036). Both groups showed an overall shift towards lower mRS scores at 6 months post-onset compared to baseline, with a more significant shift towards lower scores in the acute intervention group than the non-acute intervention group. CONCLUSIONS: In the real-world setting, acupuncture intervention in the acute phase in patients with first-ever stroke, compared to acupuncture intervention after the acute phase, reduces the risk of disability at 6 months post-onset and improves functional status.

Thermal-Rectified Gradient Porous Polymeric Film for Solar-Thermal Regulatory Cooling.

Solar-thermal regulation concerning thermal insulation and solar modulation is pivotal for cooling textiles and smart buildings. Nevertheless, a contradiction arises in balancing the demand to prevent external heat infiltration with the efficient dissipation of excess heat from enclosed spaces. Here, a concentration-gradient polymerization strategy is presented for fabricating a gradient porous polymeric film comprising interconnected polymeric microspheres. This method involves establishing an electric field-driven gradient distribution of charged crosslinkers in the precursor solution, followed by subsequent polymerization and freeze-drying processes. The resulting porous film exhibits a significant porosity gradient along its thickness, leading to exceptional unidirectional thermal insulation capabilities with a thermal rectification factor of 21%. The gradient porous film, with its thermal rectification properties, effectively reconciles the conflicting demands of diverse thermal conductivity for cooling unheated and spontaneously heated enclosed spaces. Consequently, the gradient porous film demonstrates remarkable enhancements in solar-thermal management, achieving temperature reductions of 3.0 and 4.1 °C for unheated and spontaneously heated enclosed spaces, respectively, compared to uniform porous films. The developed gradient-structured porous film thus holds promise for the development of thermal-rectified materials tailored to regulate solar-thermal conditions within enclosed environments.

The R2R3-MYB transcription factor ZeMYB32 negatively regulates anthocyanin biosynthesis in Zinnia elegans.

KEY MESSAGE: This study identified an R2R3-MYB from Zinnia elegans, ZeMYB32, which negatively regulates anthocyanin biosynthesis.

Hippuric acid alleviates dextran sulfate sodium-induced colitis via suppressing inflammatory activity and modulating gut microbiota.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease associated with metabolic disorder and gut dysbiosis. Decreased abundance of hippuric acid (HA) was found in patients with IBD. HA, metabolized directly from benzoic acid in the intestine and indirectly from polyphenols, serves as a marker of polyphenol catabolism. While polyphenols and benzoic acid have been shown to alleviate intestinal inflammation, the role of HA in this context remains unknown. Herein, we investigated the effects and mechanism of HA on DSS-induced colitis mice. The results revealed that HA alleviated clinical activity and intestinal barrier damage, decreased pro-inflammatory cytokine production. Metagenomic sequencing suggested that HA treatment restored the gut microbiota, including an increase in beneficial gut bacteria such as Adlercreutzia, Eubacterium, Schaedlerella and Bifidobacterium_pseudolongum. Furthermore, we identified 113 candidate genes associated with IBD that are potentially under HA regulation through network pharmacological analyses. 10 hub genes including ALB, IL-6, HSP90AA1, and others were identified using PPI analysis and validated using molecular docking and mRNA expression analysis. Additionally, KEGG analysis suggested that the renin-angiotensin system (RAS), NF-κB signaling and Rap1 signaling pathways were important pathways in the response of HA to colitis. Thus, HA may provide novel biotherapy options for IBD.

A Wrist-Inspired Magneto-Pneumatic Hybrid-Driven Soft Actuator with Bidirectional Torsion.

A novel wrist-inspired soft actuator, which is driven by a magneto-pneumatic hybrid system and based on a Kresling origami unit, is proposed. The geometric model, kinematic analysis model, and quasistatic analysis model of the Kresling origami unit are presented. A key focus is on the formulation and investigation of the variation in rotation angle using the kinematic analysis model. A wrist-inspired soft actuator is designed, and its quasistatic characteristics are validated through various experiments. The paper proposes an innovative magneto-pneumatic hybrid actuation method, capable of achieving bidirectional torsion. This actuation method is experimentally validated, demonstrating the actuator's ability to maintain 3 steady states and its capability for bidirectional torsion deformation. Furthermore, the paper highlights the potential of the Kresling origami unit in designing soft actuators capable of achieving large rotation angles. For instance, an actuator with 6 sides (n = 6) is shown to achieve a rotation angle of 239.5°, and its rotation ratio exceeds 277°, about twice the largest one reported in other literature. The actuator offers a practical and effective solution for bidirectional torsion deformation in soft robotic applications.

Lysine Methyltransferase 5A Promotes the Progression of Growth hormone Pituitary Neuroendocrine Tumors Through the Wnt/ß-catenin Signaling Pathway.

INTRODUCTION: Growth hormone (GH) secreting pituitary adenoma is considered one of the most harmful types of Pituitary Neuroendocrine Tumors (PitNETs). Our previous research has found that high expression of Lysine Methyltransferase 5A (KMT5A) is closely related to the proliferation of PitNETs. The aim of this study was to investigate the role and molecular mechanism of KMT5A in the progression of GH PitNETs. METHODS: Immunohistochemistry, qRT-PCR and Western blot (WB) were used to assess the expression levels of KMT5A in human normal pituitary and GH PitNETs, as well as in rat normal pituitary and GH3 cells. Additionally, we utilized RNA interference technology and treatment with a selective KMT5A inhibitor to decrease the expression of KMT5A in GH3 cells. CCK-8, EdU, Flow cytometry (FCM), clone formation, and WB assay were further employed to evaluate the impact of KMT5A on the proliferation of GH3 cells in vitro. A xenograft model was established to evaluate the role of KMT5A in GH PitNETs progression in vivo. RESULTS: KMT5A was highly expressed in GH PitNETs and GH3 cells. Moreover, the reduction of KMT5A expression led to inhibited growth of GH PitNETs and increased apoptosis of tumor cells, as indicated by the findings from CCK-8, EdU, clone formation and FCM assays. Additionally, WB analysis identified the Wnt/ß-catenin signaling pathway as a potential mechanism through which KMT5A promotes GH PitNETs progression. CONCLUSION: Our research suggests that KMT5A may facilitate the progression of GH PitNETs via the Wnt/ß-catenin signaling pathway. Therefore, KMT5A may serve as a potential therapeutic target and molecular biomarker for GH PitNETs.