Selenium supplementation elevated SELENBP1 to inhibit fibroblast activation in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a life-threatening disease induced by abnormal activation of pulmonary adventitial fibroblasts (PAFs) in the early stage. The association between selenium deficiency and PAH is not yet fully understood. In this study, we found that the serum selenium content of PAH patients was significantly lower than that of healthy volunteers in two independent cohorts. Moreover, PAH patients with lower selenium levels may present poorer prognosis. Prophylactic selenium supplementation could effectively improve hemodynamics and pulmonary vascular remodeling in monocrotaline-induced pulmonary hypertension rat models. Mechanistically, selenium supplementation restored the level of selenium binding protein 1 (SELENBP1) which could exert an antagonistic effect on PAF activation. The rescue assay further proved that selenium supplementation worked in a SELENBP1-dependent manner. These findings demonstrated that selenium deficiency is an important risk factor in PAH, and the selenium-SELENBP1 axis represents a promising target for PAH prevention.

Kirigami-Inspired Three-Dimensional Metamaterials with Programmable Isotropic and Orthotropic Thermal Expansion.

Mechanical metamaterials with specifically designed cells can provide unusual thermal expansion properties for diverse applications. Limited by very few available cell topologies and complicated non-linear structural deformation, most existing thermal expansion metamaterials can only achieve orthogonally isotropic negative/zero/positive thermal expansion (NTE/ZTE/PTE) within a mild range, especially the 3D ones. Here, based on one-degree-of-freedom kirigami polyhedrons proposed with a kinematic design strategy, a family of 3D isotropic and orthotropic metamaterials capable of programmable NTE, PTE, and even ZTE over ultra-wide range is developed. Incorporating bi-material strips as creases for isotropic polyhedrons, NTE and PTE metamaterials with coefficients of thermal expansion (CTEs) ranging from -2354.3 to 3006.7 ppm/°C are designed and programmed by the theoretical model. Meanwhile, isotropic ZTE metamaterials are constructed by either homogeneous tessellation of ZTE cells or hybrid tessellation of NTE and PTE cells. Furthermore, by allowing distinct geometric parameters in the three orthogonal directions of the kirigami polyhedrons while preserving the kinematic motion, orthotropic metamaterials, in which each of the three directions can be assigned with an independently programmed NTE, ZTE, or PTE, are also achieved. This study paves a novel pathway for the development of thermal expansion metamaterials with potential applications for space optical systems, MEMS, and so on.

Programming the mechanical properties of double-corrugated metamaterials by varying mountain-valley assignments.

Origami metamaterials have gained significant attention in recent years, with extensive analysis conducted on their mechanical properties. Previous studies have primarily focused on the effects of design angles, panel side lengths, folding angles or other geometric and material parameters. However, mountain-valley crease assignments of origami patterns, which significantly effect both the geometric and mechanical properties, have yet to be studied in depth. In this article, we create a series of double-corrugated metamaterials with diverse mountain-valley assignments and analyse their Poisson's ratios and mechanical properties under compression loading. The findings of our study demonstrate that varying the mountain-valley assignments allows for the construction of metamaterials with consistent or distinct Poisson's ratios. These assignments have the capability to program the magnitude and to vary the rate of the folding angles. Furthermore, the mechanical properties of the corresponding metamaterials, in particular the specific energy absorption (SEA) and normalized stiffness, exhibit positive correlations with the respective folding angles. Our study highlights the significance of varying mountain-valley assignments as a promising approach for designing origami metamaterials and programming their mechanical properties.This article is part of the theme issue 'Origami/Kirigami-inspired structures: from fundamentals to applications'.

Corrigendum: The effect of acupuncture at the Taiyang acupoint on visual function and EEG microstates in myopia.

[This corrects the article DOI: 10.3389/fnint.2023.1234471.].

Soft Actuator with Biomass Porous Electrode: A Strategy for Lowering Voltage and Enhancing Durability.

Electroactive artificial muscles with deformability have attracted widespread interest in the field of soft robotics. However, the design of artificial muscles with low-driven voltage and operational durability remains challenging. Herein, novel biomass porous carbon (BPC) electrodes are proposed. The nanoporous BPC enables the electrode to provide exposed active surfaces for charge transfer and unimpeded channels for ion migration, thus decreasing the driving voltage, enhancing time durability, and maintaining the actuation performances simultaneously. The proposed actuator exhibits a high displacement of 13.6 mm (bending strain of 0.54%) under 0.5 V and long-term durability of 99.3% retention after 550,000 cycles (∼13 days) without breaks. Further, the actuators are integrated to perform soft touch on a smartphone and demonstrated as bioinspired robots, including a bionic butterfly and a crawling robot (moving speed = 0.08 BL s-1). This strategy provides new insight into the design and fabrication of high-performance electroactive soft actuators with great application potential.

Comprehensive molecular classification predicted microenvironment profiles and therapy response for HCC.

BACKGROUND AND AIMS: Tumor microenvironment (TME) heterogeneity leads to a discrepancy in survival prognosis and clinical treatment response for patients with HCC. The clinical applications of documented molecular subtypes are constrained by several issues. APPROACH AND RESULTS: We integrated 3 single-cell data sets to describe the TME landscape and identified 6 prognosis-related cell subclusters. Unsupervised clustering of subcluster-specific markers was performed to generate transcriptomic subtypes. The predictive value of these molecular subtypes for prognosis and treatment response was explored in multiple external HCC cohorts and the Xiangya HCC cohort. TME features were estimated using single-cell immune repertoire sequencing, mass cytometry, and multiplex immunofluorescence. The prognosis-related score was constructed based on a machine-learning algorithm. Comprehensive single-cell analysis described TME heterogeneity in HCC. The 5 transcriptomic subtypes possessed different clinical prognoses, stemness characteristics, immune landscapes, and therapeutic responses. Class 1 exhibited an inflamed phenotype with better clinical outcomes, while classes 2 and 4 were characterized by a lack of T-cell infiltration. Classes 5 and 3 indicated an inhibitory tumor immune microenvironment. Analysis of multiple therapeutic cohorts suggested that classes 5 and 3 were sensitive to immune checkpoint blockade and targeted therapy, whereas classes 1 and 2 were more responsive to transcatheter arterial chemoembolization treatment. Class 4 displayed resistance to all conventional HCC therapies. Four potential therapeutic agents and 4 targets were further identified for high prognosis-related score patients with HCC. CONCLUSIONS: Our study generated a clinically valid molecular classification to guide precision medicine in patients with HCC.

Simultaneous removal of ammonia nitrogen, phosphate, zinc, and phenol by degradation of cellulose in composite mycelial pellet bioreactor: Enhanced performance and community co-assembly mechanism.

In this experiment, the prepared tea biochar-cellulose@LDH material (TB-CL@LDH) was combined with mycelium pellets to form the composite mycelial pellets (CMP), then assembled and immobilized with strains Pseudomonas sp. Y1 and Cupriavidus sp. ZY7 to construct a bioreactor. At the best operating parameters, the initial concentrations of phosphate (PO43--P), ammonia nitrogen (NH4+-N), chemical oxygen demand (COD), zinc (Zn2+), and phenol were 22.3, 25.0, 763.8, 1.0, and 1.0 mg L-1, the corresponding removal efficiencies were 80.4, 87.0, 83.4, 91.8, and 96.6%, respectively. Various characterization analyses demonstrated that the strain Y1 used the additional carbon source produced by the strain ZY7 degradation of cellulose to enhance the removal of composite pollutants and clarified the principle of Zn2+ and PO43--P removal by adsorption, co-precipitation and biomineralization. Pseudomonas and Cupriavidus were the dominant genera according to the high-throughput sequencing. As shown by KEGG results, nitrification and denitrification genes were affected by phenol. The study offers prospects for the simultaneous removal of complex pollutants consisting of NH4+-N, PO43--P, Zn2+, and phenol.

The effect of acupuncture at the Taiyang acupoint on visual function and EEG microstates in myopia.

Objective: Acupuncture has certain effects to improve myopia visual function, but its neural mechanism is unclear. In this study, we acupunctured at the right Taiyang acupoint of myopic patients to analyze the effects of acupuncture on visual function and electroencephalographic activity and to investigate the correlation between improvements in visual function and changes in the brain. Methods: In this study, a total of 21 myopic patients were recruited. The contrast sensitivity (CS) of the subjects was examined before and after acupuncture, and electroencephalography (EEG) data of the entire acupuncture process were recorded. Results: The study found that compared with before acupuncture, the CS of both eyes in myopic patients at each spatial frequency was increased after acupuncture; compared with the resting state, the contribution of microstate C was decreased during the post-acupuncture state, and the transition probability between microstate A and microstate C was reduced; in addition, the contribution of microstate C was negatively correlated with CS at both 12 and 18 cpd. Conclusion: The contrast sensitivity of myopic patients was improved after acupuncture at the Taiyang acupoint (20 min), which may be related to microstate C.

Enhanced ammonia nitrogen and phenol removal by immobilized bacteria through composite mycelium pellet-driven quinone redox cycle.

The composite mycelium pellet (CMP) was coupled with Pseudomonas sp. Y1 (CMP-Y1) to remove phenol and ammonia nitrogen (NH4+-N). The CMP was formed by the self-assembly of fungal mycelium with sponge iron (SIO), gallic acid (GA), and oxalic acid. The results showed that CMP with abundant pore size and successful internal loading of sponge iron containing iron nanoparticles. CMP could induce GA redox cycle to form Fenton-like reaction and thus achieve efficient phenol removal (93.32%, 24 h). Meanwhile, the removal efficiencies of phenol, NH4+-N, and chemical oxygen demand (COD) using CMP-Y1 at 12 h were 93.71, 92.40, and 89.00%, respectively. The increase in the electron transfer activity of strain Y1 by the addition of CMP could facilitate the nitrogen removal processes. In addition, high-throughput sequencing results indicated the abundance of antioxidant and repair genes was increased, which might be a strategy of strain Y1 to cope with oxidative stress. This strategy provided the possibility for the practical application of the combination of advanced oxidation and biological treatment, and offered new insights into the symbiotic system of fungi and bacteria.

A cancer-associated fibroblast subtypes-based signature enables the evaluation of immunotherapy response and prognosis in bladder cancer.

Bladder cancer (BLCA) is one of the most prevalent and heterogeneous urinary malignant tumors. Previous researches have reported a significant association between cancer-associated fibroblasts (CAFs) and poor prognosis of tumor patients. However, uncertainty surrounds the role of CAFs in the BLCA tumor microenvironment, necessitating further investigation into the CAFs-related gene signatures in BLCA. In this study, we identified three CAF subtypes in BLCA according to single-cell RNA-seq data and constructed CAFs-related risk score (CRRS) by screening 102,714 signatures. The survival analysis, ROC curves, and nomogram suggested that CRRS was a valuable predictor in 2,042 patients from 9 available public datasets and Xiangya real-world cohort. We further revealed the significant correlation between CRRS and clinicopathological characteristics, genome alterations, and epithelial-mesenchymal transition (EMT). A high CRRS indicated a non-inflamed phenotype and a lower remission rate of immunotherapy in BLCA. In conclusion, the CRRS had the potential to predict the prognosis and immunotherapy response of BLCA patients.

Multi-Stability of the Extensible Origami Structures.

Multi-stable structures and metamaterials with more than two stable states are widely applied in diversified engineering applications. Non-rigid foldable origami patterns have provided an effective way of designing multi-stable structures. But most of them have only two stable states and therefore require a combination of many units to achieve multi-stability. Here, a series of extensible origami structures are proposed with generic multi-stability based on non-rigid wrapping origami. Through a kinematic analysis and experiments, it is demonstrate that a sequential folding among different layers of the structures is created to generate a continuous rigid origami range and several discrete rigid origami states, which consequently leads to the multi-stability of the extensible origami structures. Moreover, the effects of design parameters on the mechanical properties of the structures are investigated by numerical simulation, enabling properties programmability upon specific needs. This study thus paves a new pathway for the development of novel multi-stable origami structures.

An ultrasound-based radiomics model for survival prediction in patients with endometrial cancer.

PURPOSE: To establish a nomogram integrating radiomics features based on ultrasound images and clinical parameters for predicting the prognosis of patients with endometrial cancer (EC). MATERIALS AND METHODS: A total of 175 eligible patients with ECs were enrolled in our study between January 2011 and April 2018. They were divided into a training cohort (n = 122) and a validation cohort (n = 53). Least absolute shrinkage and selection operator (LASSO) regression were applied for selection of key features, and a radiomics score (rad-score) was calculated. Patients were stratified into high risk and low-risk groups according to the rad-score. Univariate and multivariable COX regression analysis was used to select independent clinical parameters for disease-free survival (DFS). A combined model based on radiomics features and clinical parameters was ultimately established, and the performance was quantified with respect to discrimination and calibration. RESULTS: Nine features were selected from 1130 features using LASSO regression in the training cohort, which yielded an area under the curve (AUC) of 0.823 and 0.792 to predict DFS in the training and validation cohorts, respectively. Patients with a higher rad-score were significantly associated with worse DFS. The combined nomogram, which was composed of clinically significant variables and radiomics features, showed a calibration and favorable performance for DFS prediction (AUC 0.893 and 0.885 in the training and validation cohorts, respectively). CONCLUSION: The combined nomogram could be used as a tool in predicting DFS and may assist individualized decision making and clinical treatment.

Lipophagy-related gene RAB7A is involved in immune regulation and malignant progression in hepatocellular carcinoma.

BACKGROUND: RAB7A (RAS-related in Brain 7A) is an important member of the RAS oncogene family. However, the correlation between RAB7A and the development and immune infiltration of hepatocellular carcinoma (HCC) has rarely been studied. Here, we studied the role of RAB7A in HCC through bioinformatics analysis, real-world cohort validation, and in vitro experimental exploration. MATERIALS AND METHODS: The RAB7A expression level was analyzed through TCGA, HPA and TISIDB databases. TIMER and TISCH were used to analyze the correlation between RAB7A and tumor immune microenvironment. The expression of RAB7A was detected through real-time PCR and western blotting. The cell proliferation was detected by EdU and CCK8. Wound-healing and transwell assays were used to test the invasion and migration ability. Cell cycle distribution and reactive oxygen species (ROS) content were analyzed by flow cytometry. Identification of epithelial-mesenchymal transition (EMT) was performed by immunofluorescence double staining. Immunohistochemistry (IHC) was used to evaluate the correlation between RAB7A and immune checkpoints. RESULTS: RAB7A is upregulated in most of the tumor types, and the upregulation of RAB7A is associated with a poorer prognosis in many cancers. The results showed that RAB7A was significantly positively correlated with the infiltration of macrophages and cancer-associated fibroblasts (CAFs), but negatively correlated with M2-type macrophages in most tumors. The single-cell atlas also revealed the distribution and proportion of RAB7A in immune cells of HCC. The in vitro experiments suggested that RAB7A was increased in HCC tissue and cell lines. The knockdown of RAB7A inhibited the activation of the PIK3CA-AKT pathway and suppressed the expression of CDK4, CDK6 and CCNA2. Knockdown of RAB7A induced G0/G1 arrest and ROS accumulation in HCC. In addition, overexpression of RAB7A enhanced migration and invasion by inducing EMT. The real-world cohort showed that the expression level of RAB7A was positively correlated with the expression levels of TGFBR1 and PD-L1. CONCLUSIONS: RAB7A may serve as a potential tumor prognostic and immune infiltration-related biomarker, predicting immunotherapy efficacy in certain cancer types, especially in HCC. Besides, RAB7A was a multi-pathway target involved in the malignant progression of HCC.

RASGRP2 is a potential immune-related biomarker and regulates mitochondrial-dependent apoptosis in lung adenocarcinoma.

Background: Ras guanine nucleotide-releasing protein 2 (RASGRP2), one of the guanine nucleotide exchange factors (GEFs), has attracted much attention in recent years. However, the correlation between RASGRP2 and immune infiltration and malignant features in lung adenocarcinoma (LUAD) has rarely been mentioned. Methods: The Limma package and the LASSO regression model were performed to screen for differentially expressed genes. Data from the TCGA and 5 GEO databases were used to explore the expression level of RASGRP2 in LUAD patients. A weighted co-expression network and LinkFinder module were established to find the related genes of RASGRP2. The ESTIMATE algorithm was used to analyze the correlation between RASGRP2 and immune infiltration in LUAD. Tumor-infiltrating immune cells were sorted and sequenced at the single-cell level to analyze differences in RASGRP2. Real-time PCR and immunohistochemistry were performed in the real-world cohort to verify the expression of RASGRP2 and its correlation with immune-related genes. Clone formation and EdU assays were used to verify the proliferation ability. The proportion of apoptotic cells was analyzed by flow cytometry. Observation of mitochondrial membrane potential (MMP) changes by fluorescence microscopy. Results: Our results suggested that decreased RASGRP2 was associated with worse clinical parameters and prognosis in LUAD patients. And we constructed a FLI1-HSA-miR-1976-RASGRP2 transcriptional network to support the role of RASGRP2. Enrichment analysis revealed that RASGRP2 was involved in lymphocyte activation and leukocyte adhesion. RASGRP2 was found to be positively correlated with the infiltration of most immune cells, immunoregulators, and chemokines in a subsequent study. Meanwhile, the real-world cohort confirmed that the expression levels of PDCD1, CTLA4, CD40LG, CCL14, CXCR5, and CCR7 were higher in the high-RASGRP2 expression group. Cytological experiments proved that RASGRP2 inhibited cell proliferation in LUAD by regulating mitochondrial-dependent apoptosis. Conclusion: RASGRP2 was a potential immune-related biomarker of LUAD. In addition, RASGRP2 was involved in the malignant progression of LUAD through the regulation of mitochondrial-dependent apoptosis.

Prognostic stratification based on m5C regulators acts as a novel biomarker for immunotherapy in hepatocellular carcinoma.

Background: Immunotherapy is a promising anti-cancer strategy in hepatocellular carcinoma (HCC). However, a limited number of patients can benefit from it. There are currently no reliable biomarkers available to find the potential beneficiaries. Methylcytosine (m5C) is crucial in HCC, but its role in forecasting clinical responses to immunotherapy has not been fully clarified. Methods: In this study, we analyzed 371 HCC patients from The Cancer Genome Atlas (TCGA) database and investigated the expression of 18 m5C regulators. We selected 6 differentially expressed genes (DEGs) to construct a prognostic risk model as well as 2 m5C-related diagnostic models. Results: The 1-, 3-, and 5-year area under the curve (AUC) of m5C scores for the overall survival (OS) was 0.781/0.762/0.711, indicating the m5C score system had an ideal distinction of prognostic prediction for HCC. The survival analysis showed that patients with high-risk scores present a worse prognosis than the patients with low-risk scores (p< 0.0001). We got consistent results in 6 public cohorts and validated them in Xiangya real-world cohort by quantitative real-time PCR and immunohistochemical (IHC) assays. The high-m5C score group was predicted to be in an immune evasion state and showed low sensitivity to immunotherapy, but high sensitivity to chemotherapy and potential targeted drugs and agents, such as sepantronium bromide (YM-155), axitinib, vinblastine and docetaxel. Meanwhile, we also constructed two diagnostic models to distinguish HCC tumors from normal liver tissues or liver cirrhosis. Conclusion: In conclusion, our study helps to early screen HCC patients and select patients who can benefit from immunotherapy. Step forwardly, for the less likely beneficiaries, this study provides them with new potential targeted drugs and agents for choice to improve their prognosis.

A Humidity-Powered Soft Robot with Fast Rolling Locomotion.

A range of soft robotic systems have recently been developed that use soft, flexible materials and respond to environmental stimulus. The greatest challenge in their design is the integration of the actuator, energy sources, and body of robots while achieving fast locomotion and well-defined programmable trajectories. This work presents such a design that operates under constant conditions without the need for an externally modulated stimulus. By using a humidity-sensitive agarose film and overcoming the isotropic and random bending of the film, the robot, which we call the Hydrollbot, harnesses energy from evaporation for spontaneous and continuous fast self-rolling locomotion with a programmable trajectory in a constant-humidity environment. Moreover, the geometric parameters of the film were fine-tuned to maximize the rolling speed, and the optimised hydrollbot is capable of carrying a payload up to 100% of its own weight. The ability to self-propel fast under constant conditions with programmable trajectories will confer practical advantages to this robot in the applications for sensors, medical robots, actuation, etc.

Kirigami-based metastructures with programmable multistability.

SignificanceDifferent from most existing multistable structures whose multiple stable states are achieved through the combinational effect of bistable units, we invent a generic tristable kirigami cuboid. The three stable states have fundamentally distinct geometric configurations and chirality, and the transformation among them can be realized by tension/compression or clockwise/counterclockwise twist. Tessellating the units in series, a family of multistable metamaterials can be constructed, the mechanical behaviors of which are programmable by the unit geometry, the material of the elastic joints, the number of units, and the loading conditions. As a demonstration of the potential applications, a frequency reconfigurable antenna for 5G triple-band communication is developed based on a tristable unit, and the frequency tunability is verified by experiments.

The role of the tumor microbe microenvironment in the tumor immune microenvironment: bystander, activator, or inhibitor?

The efficacy of cancer immunotherapy largely depends on the tumor microenvironment, especially the tumor immune microenvironment. Emerging studies have claimed that microbes reside within tumor cells and immune cells, suggesting that these microbes can impact the state of the tumor immune microenvironment. For the first time, this review delineates the landscape of intra-tumoral microbes and their products, herein defined as the tumor microbe microenvironment. The role of the tumor microbe microenvironment in the tumor immune microenvironment is multifaceted: either as an immune activator, inhibitor, or bystander. The underlying mechanisms include: (I) the presentation of microbial antigens by cancer cells and immune cells, (II) microbial antigens mimicry shared with tumor antigens, (III) microbe-induced immunogenic cell death, (IV) microbial adjuvanticity mediated by pattern recognition receptors, (V) microbe-derived metabolites, and (VI) microbial stimulation of inhibitory checkpoints. The review further suggests the use of potential modulation strategies of the tumor microbe microenvironment to enhance the efficacy and reduce the adverse effects of checkpoint inhibitors. Lastly, the review highlights some critical questions awaiting to be answered in this field and provides possible solutions. Overall, the tumor microbe microenvironment modulates the tumor immune microenvironment, making it a potential target for improving immunotherapy. It is a novel field facing major challenges and deserves further exploration.

Folding of Tubular Waterbomb.

Origami has recently emerged as a promising building block of mechanical metamaterials because it offers a purely geometric design approach independent of scale and constituent material. The folding mechanics of origami-inspired metamaterials, i.e., whether the deformation involves only rotation of crease lines (rigid origami) or both crease rotation and facet distortion (nonrigid origami), is critical for fine-tuning their mechanical properties yet very difficult to determine for origami patterns with complex behaviors. Here, we characterize the folding of tubular waterbomb using a combined kinematic and structural analysis. We for the first time uncover that a waterbomb tube can undergo a mixed mode involving both rigid origami motion and nonrigid structural deformation, and the transition between them can lead to a substantial change in the stiffness. Furthermore, we derive theoretically the range of geometric parameters for the transition to occur, which paves the road to program the mechanical properties of the waterbomb pattern. We expect that such analysis and design approach will be applicable to more general origami patterns to create innovative programmable metamaterials, serving for a wide range of applications including aerospace systems, soft robotics, morphing structures, and medical devices.