Discovery and mechanism explanation of a novel green biocatalyst esterase Bur01 from Burkholderia ambifaria for ester synthesis under aqueous phase.

Biocatalyst catalyzing the synthesis of esters under aqueous phase is an alternative with green and sustainable characteristics. Here, a biocatalyst esterase Bur01 was identified through genome sequencing and gene library construction from a Burkholderia ambifaria BJQ0010 with efficient ester synthesis property under aqueous phase for the first time. Bur01 was soluble expressed and the purified enzyme showed the highest activity at pH 4.0 and 40 °C. It had a broad substrate spectrum, especially for ethyl esters. The structure of Bur01 was categorized as a member of α/ß fold hydrolase superfamily. The easier opening of lid under aqueous phase and the hydrophobicity of substrate channel contribute to easier access to the active center for substrate. Molecular docking and site-directed mutation demonstrated that the oxyanion hole Ala22, Met112 and π-bond stacking between His24 and Phe217 played essential roles in catalytic function. The mutants V149A, V149I, L159I and F137I enhanced enzyme activity to 1.42, 1.14, 1.32 and 2.19 folds due to reduced spatial resistance and increased hydrophobicity of channel and ethyl octanoate with the highest conversion ratio of 68.28 % was obtained for F137I. These results provided new ideas for developing green catalysts and catalytic basis of mechanistic studies for ester synthetase under aqueous phase.

Gustatory Receptor 206 Participates in the Foraging Behavior of Larvae of Polyphagous Pest Spodoptera litura.

Insect gustatory receptors (GRs) aid in the precise identification of deterrent or stimulant compounds associated with food, mating, and egg-laying. Thus, they are promising targets for developing efficient insecticides. Here, 61 GRs in the chemosensory organs of Spodoptera litura larvae and adults were identified. Among them, SlitGR206 exhibited larval labium (LL)-specific expression characteristics. To explore the role of SlitGR206, a bacterial expression system was established to produce high-quality double-stranded RNA (dsRNA) and suppress SlitGR206 expression in LL. Subsequent behavioral assessments revealed that SlitGR206 silencing influenced larval feeding preferences and absorption. Moreover, it was found to reduce the ability of larvae to forage the five crucial host odorants. These findings demonstrate that SlitGR206 likely plays an indirect regulatory role in host recognition, consequently affecting foraging behavior. This provides a crucial foundation for the analysis of functional diversity among insect GRs and the precise development of nucleic acid pesticides in the future.

Prediction analysis of carbon emission in China's electricity industry based on the dual carbon background.

The electric power sector is the primary contributor to carbon emissions in China. Considering the context of dual carbon goals, this paper examines carbon emissions within China's electricity sector. The research utilizes the LMDI approach for methodological rigor. The results show that the cumulative contribution of economies scale, power consumption factors and energy structure are 114.91%, 85.17% and 0.94%, which contribute to the increase of carbon emissions, the cumulative contribution of power generation efficiency and ratio of power dissipation to generation factor are -19.15% and -0.01%, which promotes the carbon reduction. The decomposition analysis highlights the significant influence of economic scale on carbon emissions in the electricity industry, among the seven factors investigated. Meanwhile, STIRPAT model, Logistic model and GM(1,1) model are used to predict carbon emissions, the average relative error between actual carbon emissions and the predicted values are 0.23%, 8.72% and 7.05%, which indicates that STIRPAT model is more suitable for medium- to long-term predictions. Based on these findings, the paper proposes practical suggestions to reduce carbon emissions and achieve the dual carbon goals of the power industry.

TGF-ß downstream of Smad3 and MAPK signaling antagonistically regulate the viability and partial epithelial-mesenchymal transition of liver progenitor cells.

BACKGROUND: Liver progenitor cells (LPCs) are a subpopulation of cells that contribute to liver regeneration, fibrosis and liver cancer initiation under different circumstances. RESULTS: By performing adenoviral-mediated transfection, CCK-8 analyses, F-actin staining, transwell analyses, luciferase reporter analyses and Western blotting, we observed that TGF-ß promoted cytostasis and partial epithelial-mesenchymal transition (EMT) in LPCs. In addition, we confirmed that TGF-ß activated the Smad and MAPK pathways, including the Erk, JNK and p38 MAPK signaling pathways, and revealed that TGFß-Smad signaling induced growth inhibition and partial EMT, whereas TGFß-MAPK signaling had the opposite effects on LPCs. We further found that the activity of Smad and MAPK signaling downstream of TGF-ß was mutually restricted in LPCs. Mechanistically, we found that TGF-ß activated Smad signaling through serine phosphorylation of both the C-terminal and linker regions of Smad2 and 3 in LPCs. Additionally, TGFß-MAPK signaling inhibited the phosphorylation of Smad3 but not Smad2 at the C-terminus, and it reinforced the linker phosphorylation of Smad3 at T179 and S213. We then found that overexpression of mutated Smad3 at linker phosphorylation sites intensifies TGF-ß-induced cytostasis and EMT, mimicking the effects of MAPK inhibition in LPCs, whereas mutation of Smad3 at the C-terminus caused LPCs to blunt TGF-ß-induced cytostasis and partial EMT. CONCLUSION: These results suggested that TGF-ß downstream of Smad3 and MAPK signaling were mutually antagonistic in regulating the viability and partial EMT of LPCs. This antagonism may help LPCs overcome the cytostatic effect of TGF-ß under fibrotic conditions and maintain partial EMT and progenitor phenotypes.

Analysis of differences in microorganisms and aroma profiles between normal and off-flavor pit mud in Chinese strong-flavor Baijiu.

The unique cellar fermentation process of Chinese strong-flavor Baijiu is the reason for its characteristic cellar aroma flavor. The types, abundance, community structure and metabolic activity of microorganisms in the pit mud directly affect the microbial balance in the white spirit production environment, promoting the formation of typical aromas and influencing the quality of CFSB. During the production process, the production of off-flavor in the cellar may occur. The aim of this study is to elucidate the differences in microbiota and flavor between normal pit mud and abnormal pit mud (pit mud with off-flavor). A total of 46 major volatile compounds were identified, and 24 bacterial genera and 21 fungal genera were screened. The esters, acids, and alcohols in the abnormal pit mud were lower than those in the normal pit mud, while the aldehydes were higher. 3-Methyl indole, which has been proven to be responsible for the muddy and musty flavors, was detected in both types of pit mud, and for the first time, high levels of 4-methylanisole was detected in the pit mud. The microbial composition of the two types of pit mud showed significant differences in the bacterial genera of Sporosarcina, Lactobacillus, Garciella, Anaerosalibacter, Lentimicrobium, HN-HF0106, Petrimonas, Clostridium_sensu_stricto_12 and Bacillus, and the fungal genera of Millerozyma, Penicillium, Mortierella, Monascus, Saccharomyces, Issatchenkia, Pithoascus, Pseudallescheria, and Wickerhamomyces. Additionally, we speculate that Sporosarcina is the predominant bacterial genus responsible for the imbalance of microbiota in pit mud.

GRIN2A mutation is a novel indicator of stratifying beneficiaries of immune checkpoint inhibitors in multiple cancers.

Glutamate-NMDAR receptors (GRINs) have been reported to influence cancer immunogenicity; however, the relationship between GRIN alterations and the response to immune checkpoint inhibitors (ICIs) has not been determined. This study combined clinical characteristics and mutational profiles from multiple cohorts to form a discovery cohort (n = 901). The aim of this study was to investigate the correlation between the mutation status of the GRIN gene and the response to ICI therapy. Additionally, an independent ICI-treated cohort from the Memorial Sloan Kettering Cancer Center (MSKCC, N = 1513) was used for validation. Furthermore, this study explored the associations between GRIN2A mutations and intrinsic and extrinsic immunity using multiomics analysis. In the discovery cohort, patients with GRIN2A-MUTs had improved clinical outcomes, as indicated by a higher objective response rate (ORR: 36.8% vs 25.8%, P = 0.020), durable clinical benefit (DCB: 55.2% vs 38.7%, P = 0.005), prolonged progression-free survival (PFS: HR = 0.65; 95% CI 0.49 to 0.87; P = 0.003), and increased overall survival (OS: HR = 0.67; 95% CI 0.50 to 0.89; P = 0.006). Similar results were observed in the validation cohort, in which GRIN2A-MUT patients exhibited a significant improvement in overall survival (HR = 0.66; 95% CI = 0.49 to 0.88; P = 0.005; adjusted P = 0.045). Moreover, patients with GRIN2A-MUTs exhibited an increase in tumor mutational burden, high expression of costimulatory molecules, increased activity of antigen-processing machinery, and infiltration of various immune cells. Additionally, gene sets associated with cell cycle regulation and the interferon response were enriched in GRIN2A-mutated tumors. In conclusion, GRIN2A mutation is a novel biomarker associated with a favorable response to ICIs in multiple cancers.

Targeting MMP9 in CTNNB1 mutant hepatocellular carcinoma restores CD8+ T cell-mediated antitumour immunity and improves anti-PD-1 efficacy.

OBJECTIVE: The gain of function (GOF) CTNNB1 mutations (CTNNB1 GOF ) in hepatocellular carcinoma (HCC) cause significant immune escape and resistance to anti-PD-1. Here, we aimed to investigate the mechanism of CTNNB1 GOF HCC-mediated immune escape and raise a new therapeutic strategy to enhance anti-PD-1 efficacy in HCC. DESIGN: RNA sequencing was performed to identify the key downstream genes of CTNNB1 GOF associated with immune escape. An in vitro coculture system, murine subcutaneous or orthotopic models, spontaneously tumourigenic models in conditional gene-knock-out mice and flow cytometry were used to explore the biological function of matrix metallopeptidase 9 (MMP9) in tumour progression and immune escape. Single-cell RNA sequencing and proteomics were used to gain insight into the underlying mechanisms of MMP9. RESULTS: MMP9 was significantly upregulated in CTNNB1 GOF HCC. MMP9 suppressed infiltration and cytotoxicity of CD8+ T cells, which was critical for CTNNB1 GOF to drive the suppressive tumour immune microenvironment (TIME) and anti-PD-1 resistance. Mechanistically, CTNNB1 GOF downregulated sirtuin 2 (SIRT2), resulting in promotion of ß-catenin/lysine demethylase 4D (KDM4D) complex formation that fostered the transcriptional activation of MMP9. The secretion of MMP9 from HCC mediated slingshot protein phosphatase 1 (SSH1) shedding from CD8+ T cells, leading to the inhibition of C-X-C motif chemokine receptor 3 (CXCR3)-mediated intracellular of G protein-coupled receptors signalling. Additionally, MMP9 blockade remodelled the TIME and potentiated the sensitivity of anti-PD-1 therapy in HCC. CONCLUSIONS: CTNNB1 GOF induces a suppressive TIME by activating secretion of MMP9. Targeting MMP9 reshapes TIME and potentiates anti-PD-1 efficacy in CTNNB1 GOF HCC.

Case Report: Successful conversion and salvage resection of huge hepatocellular carcinoma with portal vein tumor thrombosis and intrahepatic metastasis via sequential hepatic arterial infusion chemotherapy, lenvatinib plus PD-1 antibody followed by simultaneous transcatheter arterial chemoembolization, and portal vein embolization.

Background: Advanced hepatocellular carcinoma (HCC) shows poor prognosis. Combined hepatic artery infusion chemotherapy (HAIC) and lenvatinib and PD-1 antibody therapy show promising effects in treating advanced HCC, and salvage hepatectomy further promotes the overall survival in patients who were successfully converted after combined therapy. However, salvage major hepatectomy is not always amenable due to insufficient future liver remnant volume (FLV). Case presentation: We report the case of a 59-year-old man with a huge HCC as well as multiple intrahepatic foci and portal vein tumor thrombosis at his right hemi-liver. Genomic and pathologic analyses of HCC tissue revealed a TMB-high, TPS, and CPS-high cancer, with mutated DNA damage repair gene FANCC. These results suggested that this patient may benefit from chemotherapy and immunotherapy. Thus, he received combined HAIC, lenvatinib, and PD-1 antibody treatment and showed a quick and durable response. After successful downstaging, this patient was evaluated as not suitable for salvage hepatectomy due to the low FLV. He then received simultaneous transcatheter arterial chemoembolization (TACE) and portal vein embolization (PVE). The FLV increased to meet the criteria of salvage hepatectomy. Finally, this patient underwent right hemi-hepatectomy without any severe perioperative complications. In addition, no tumor recurrence occurred during the 9-month follow-up period after surgery. Conclusion: Combined HAIC, lenvatinib, and PD-1 antibody therapy, followed by simultaneous TACE and PVE, is a safe and effective conversion therapy that promotes tumor necrosis and increase FLV in patients with advanced HCC.

Case Report: Durable complete response of metastatic hepatocellular carcinoma with asymptomatic hyperamylasemia to combined immunotherapy of anti-cytotoxic T lymphocyte-associated antigen 4 plus anti-programmed cell death-1 antibodies.

Background: Combined immunotherapy has shown promising results in the treatment of advanced HCC, whereas the priority population that would respond to the combined immunotherapy is still elusive. In addition, HCC with asymptomatic hyperamylasemia was not reported previously. Case presentation: An aged patient was diagnosed as HCC with BCLC stage C (bone metastasis). Notably, this patient showed asymptomatic hyperamylasemia. The patient was then enrolled in a trial evaluating combined immunotherapy of anti-PD-1 antibody sintilimab (IBI308) plus anti-CTLA-4 antibody (IBI310) in advanced HCC. After being treated with combined immunotherapy, this patient rapidly achieved complete response (CR) according to mRECIST criteria or immune partial response (iPR) according to iRECIST criteria and maintain the CR state for more than 12 months. Interestingly, serum levels of amylase and lipase in this patient were reduced after treatment. Conclusion: We reported, for the first time, a case of metastatic HCC with asymptomatic hyperamylasemia, and suggested that HCC patients with asymptomatic hyperamylasemia may benefit from combined immunotherapy of anti-CTLA-4 and PD-1 antibodies.

Glycyrrhizin inhibits LPS-induced inflammatory responses in goat ruminal epithelial cells in vitro.

Inflammation plays a crucial role in the progression of Subacute Ruminal Acidosis (SARA). The experiment was designed to investigate anti-inflammatory effects of glycyrrhizin on goats ruminal epithelial cells (GREC) which were induced SARA by Lipopolysaccharide (LPS) in vitro. The GREC were induced SARA by adding LPS at the concentration of 5 µm and glycyrrhizin was added at different concentration of 0, 60, 90, 120, 150 µm. The structural integrity of LPS-induced GREC with the treatment of glycyrrhizin were observed by electron microscope; The levels of inflammatory factors TNF-α, IL-1ß, IL-6, IL-8 and IL-12 were measured by ELISA; The number of Zo-1 and Occludin were measured, the expression of tight junction protein Occludin were measured by Western blot, and the mRNA expression of NF-κB, TNF-α, IL-1ß, IL-6, IL-8 and IL-12 were measured in vitro. The results showed that higher concentration treatment of glycyrrhizin led to better morphology in LPS-induced GREC. Glycyrrhizin inhibited the growth of inflammatory factors TNF-α, IL-1ß, IL-6, IL-8 and IL-12 in a dose-dependent manner. The number of ZO-1 and Occludin increased with the increase of adding of glycyrrhizin. Western blot analysis showed that the expression of tight junction protein Occludin in LPS-induced GREC increased with the adding of glycyrrhizin in a dose-dependent manner. Furthermore, the mRNA expression of NF-κB, TNF-α, IL-1ß, IL-6, IL-8 and IL-12 decreased significantly with the increase treatment of glycyrrhizin. Glycyrrhizin significantly inhibits LPS-induced inflammatory mediators in GREC and the effects are better with the increase treatment of glycyrrhizin in vitro.

A Deep Learning Framework for Soft Robots with Synthetic Data.

Data-driven methods with deep neural networks demonstrate promising results for accurate modeling in soft robots. However, deep neural network models rely on voluminous data in discovering the complex and nonlinear representations inherent in soft robots. Consequently, while it is not always possible, a substantial amount of effort is required for data acquisition, labeling, and annotation. This article introduces a data-driven learning framework based on synthetic data to circumvent the exhaustive data collection process. More specifically, we propose a novel time series generative adversarial network with a self-attention mechanism, Transformer TimeGAN (TTGAN) to precisely learn the complex dynamics of a soft robot. On top of that, the TTGAN is incorporated with a conditioning network that enables it to produce synthetic data for specific soft robot behaviors. The proposed framework is verified on a widely used pneumatic-based soft gripper as an exemplary experimental setup. Experimental results demonstrate that the TTGAN generates synthetic time series data with realistic soft robot dynamics. Critically, a combination of the synthetic and only partially available original data produces a data-driven model with estimation accuracy comparable to models obtained from using complete original data.

Tubular cell transcriptional intermediary factor 1γ deficiency exacerbates kidney injury-induced tubular cell polyploidy and fibrosis.

Tubulointerstitial fibrosis is considered the final convergent pathway of progressive chronic kidney diseases (CKD) regardless of etiology. However, mechanisms underlying kidney injury-induced fibrosis largely remain unknown. Recent studies have indicated that transcriptional intermediary factor 1γ (TIF1γ) inhibits the progression of fibrosis in other organs. Here, we found that TIF1γ was highly expressed in the cytoplasm and nucleus of the kidney proximal tubule. Interestingly, we found tubular TIF1γ expression was decreased in patients with CKD, including those with diabetes, hypertension, and IgA nephropathy, and in mouse models with experimental kidney fibrosis (unilateral ureteral obstruction [UUO], folic acid nephropathy [FAN], and aristolochic acid-induced nephrotoxicity). Tubule-specific knock out of TIF1γ in mice exacerbated UUO- and FAN-induced tubular cell polyploidy and subsequent fibrosis, whereas overexpression of kidney TIF1γ protected mice against kidney fibrosis. Mechanistically, in tubular epithelial cells, TIF1γ exerted an antifibrotic role via transforming growth factor-ß (TGF-ß)-dependent and -independent signaling. TIF1γ hindered TGF-ß signaling directly by inhibiting the formation and activity of the transcription factor Smad complex in tubular cells, and we discovered that TIF1γ suppressed epidermal growth factor receptor (EGFR) signaling upstream of TGF-ß signaling in tubular cells by ubiquitylating EGFR at its lysine 851/905 sites thereby promoting EGFR internalization and lysosomal degradation. Pharmacological inhibition of EGFR signaling attenuated exacerbated polyploidization and the fibrotic phenotype in mice with tubule deletion of TIF1γ. Thus, tubular TIF1γ plays an important role in kidney fibrosis by suppressing profibrotic EGFR and TGF-ß signaling. Hence, our findings suggest that maintaining homeostasis of tubular TIF1γ may be a new therapeutic option for treating tubulointerstitial fibrosis and subsequent CKD.

Hydroxyethyl starch stabilized copper-diethyldithiocarbamate nanocrystals for cancer therapy.

Cancer stem cells (CSCs) have been recognized as the culprit for tumor progression, treatment resistance, metastasis, and recurrence while redox homeostasis represents the Achilles' Heel of CSCs. However, few drugs or formulations that are capable of elevating oxidative stress have achieved clinical success for eliminating CSCs. Here, we report hydroxyethyl starch stabilized copper-diethyldithiocarbamate nanoparticles (CuET@HES NPs), which conspicuously suppress CSCs not only in vitro but also in numerous tumor models in vivo. Furthermore, CuET@HES NPs effectively inhibit CSCs in fresh tumor tissues surgically excised from hepatocellular carcinoma patients. Mechanistically, we uncover that hydroxyethyl starch stabilized copper-diethyldithiocarbamate nanocrystals via copper­oxygen coordination interactions, thereby promoting copper-diethyldithiocarbamate colloidal stability, cellular uptake, intracellular reactive oxygen species production, and CSCs apoptosis. As all components are widely used in clinics, CuET@HES NPs represent promising treatments for CSCs-rich solid malignancies and hold great clinical translational potentials. This study has critical implications for design of CSCs targeting nanomedicines.

A novel lonidamine derivative targeting mitochondria to eliminate cancer stem cells by blocking glutamine metabolism.

Cancer stem cells (CSCs) have been blamed as the main culprit of tumor initiation, progression, metastasis, chemoresistance, and recurrence. However, few anti-CSCs agents have achieved clinical success so far. Here we report a novel derivative of lonidamine (LND), namely HYL001, which selectively and potently inhibits CSCs by targeting mitochondria, with 380-fold and 340-fold lower IC50 values against breast cancer stem cells (BCSCs) and hepatocellular carcinoma stem cells (HCSCs), respectively, compared to LND. Mechanistically, we reveal that HYL001 downregulates glutaminase (GLS) expression to block glutamine metabolism, blunt tricarboxylic acid cycle, and amplify mitochondrial oxidative stress, leading to apoptotic cell death. Therefore, HYL001 displays significant antitumor activity in vivo, both as a single agent and combined with paclitaxel. Furthermore, HYL001 represses CSCs of fresh tumor tissues derived from liver cancer patients. This study provides critical implications for CSCs biology and development of potent anti-CSCs drugs.

Universal Kardar-Parisi-Zhang transient diffusion in nonequilibrium anharmonic chains.

The well known nonlinear fluctuating hydrodynamics theory has grouped diffusions in anharmonic chains into two universality classes: one is the Kardar-Parisi-Zhang (KPZ) class for chains with either asymmetric potential or nonzero static pressure and the other is the Gaussian class for chains with symmetric potential at zero static pressure, such as Fermi-Pasta-Ulam-Tsingou (FPUT)-ß chains. However, little is known of the nonequilibrium transient diffusion in anharmonic chains. Here, we reveal that the KPZ class is the only universality class for nonequilibrium transient diffusion, manifested as the KPZ scaling of the side peaks of momentum correlation (corresponding to the sound modes correlation), which was completely unexpected in equilibrium FPUT-ß chains. The underlying mechanism is that the nonequilibrium soliton dynamics cause nonzero transient pressure so that the sound modes satisfy approximately the noisy Burgers equation, in which the collisions of solitons was proved to yield the KPZ dynamic exponent of the soliton dispersion. Therefore, the unexpected KPZ universality class is obtained in the nonequilibrium transient diffusion in FPUT-ß chains and the corresponding carriers of nonequilibrium transient diffusion are attributed to solitons.

Imaginal disc growth factor is involved in melanin synthesis and energy metabolism in Bombyx mori.

The imaginal disc growth factor (IDGF), belonging to the glycoside hydrolase 18 family, plays an important role in various physiological processes in insects. However, the detail physiological function of IDGF is still unclear. In this study, transcriptome analysis was performed on the fatbody isolated from staged control and BmIDGF mutant silkworm larvae. Transcriptional profiling revealed that the absence of BmIDGF significantly affected differentially expressed genes involved in tyrosine and purine metabolism, as well as multiple energy metabolism pathways, including glycolysis, galactose, starch, and sucrose metabolism. The interruption of BmIDGF caused similar and specific gene expression changes to male and female fatbody. Furthermore, a genome-scale metabolic network integrating metabolomic and transcriptomic datasets revealed 11 pathways significantly altered at the transcriptional and metabolic levels, including amino acid, carbohydrate, uric acid metabolism pathways, insect hormone biosynthesis, and ABC transporters. In conclusion, this multiomics analysis suggests that IDGF is involved in gene-metabolism interactions, revealing its unique role in melanin synthesis and energy metabolism. This study provides new insights into the physiological function of IDGF in insects.

Does H3K27M Mutation Impact Survival Outcome of High-Grade Spinal Cord Astrocytoma?

OBJECTIVE: To evaluate the impact of H3K27M mutation in the prognosis of histological high-grade intramedullary astrocytoma. METHODS: A total of 78 patients who were diagnosed with high-grade spinal cord astrocytoma were included. Clinical data consisting demographic, radiological, molecular features and treatment data were recorded. Univariate and multivariate Cox analysis were performed to investigate variables associated with survival outcome of histological high-grade spinal cord astrocytoma. RESULTS: Median survival time was 21 months. Overall survival (OS) at 1 and 3 years was 65.7% and 40.7%, respectively. Sex, location, and tumor span did not present significant association with OS. Patients with H3K27M mutation showed significant shorter duration of symptom than patients with H3K27 wild-type. As respect to adjuvant treatment, adjuvant radiotherapy and chemotherapy were associated with favorable OS (both p = 0.01). Younger patients (age ≤ 18 years) had shorter OS (p = 0.008) than adult patients (age > 18 years). Of note, H3K27M mutation did not show significant impact on the survival outcome, regardless of histology grade 3 or grade 4 (p = 0.3). CONCLUSION: Histological high-grade spinal cord astrocytoma has dismal prognosis. Our study demonstrated that H3K27M mutation did not show significant impact on survival outcome of histological high-grade spinal cord astrocytoma.

Water-Holding Properties of Clinoptilolite/Sodium Polyacrylate-Modified Compacted Clay Cover of Tailing Pond.

Clinoptilolite and sodium polyacrylate (Na-PAA) were used as water-retaining agents to improve the water-holding capacity of compacted clay cover (CCC). The optimum moisture content and Atterberg limits of the CCC modified by clinoptilolite and Na-PAA were studied. The soil-water characteristic curve (SWCC) of the CCC modified by clinoptilolite and Na-PAA was studied. The mesostructure of the CCC was analyzed by polarized light microscopy. The test results show that: (1) the optimum moisture content and liquid limit of the CCC modified by clinoptilolite and Na-PAA increased, while the maximum dry density decreased; (2) the SWCC of the CCC modified by clinoptilolite and Na-PAA shifts to the upper right, and the volume moisture content of modified CCC is higher than that of unmodified CCC under the same matrix suction; (3) compared with the unmodified CCC, the air-entry value (AEV) of the clinoptilolite-modified CCC increased by 65.18% at most, and the AEV of the further modified CCC with Na-PAA in-creased by about two times; and (4) the flocculation structure and porosity of modified CCC decreased, and the porosity was distributed uniformly.

TRIM proteins in hepatocellular carcinoma.

The tripartite motif (TRIM) protein family is a highly conserved group of E3 ligases with 77 members known in the human, most of which consist of a RING-finger domain, one or two B-box domains, and a coiled-coil domain. Generally, TRIM proteins function as E3 ligases to facilitate specific proteasomal degradation of target proteins. In addition, E3 ligase independent functions of TRIM protein were also reported. In hepatocellular carcinoma, expressions of TRIM proteins are both regulated by genetic and epigenetic mechanisms. TRIM proteins regulate multiple biological activities and signaling cascades. And TRIM proteins influence hallmarks of HCC. This review systematically demonstrates the versatile roles of TRIM proteins in HCC and helps us better understand the molecular mechanism of the development and progression of HCC.

Robust Multimodal Indirect Sensing for Soft Robots Via Neural Network-Aided Filter-Based Estimation.

Sensory data are critical for soft robot perception. However, integrating sensors to soft robots remains challenging due to their inherent softness. An alternative approach is indirect sensing through an estimation scheme, which uses robot dynamics and available measurements to estimate variables that would have been measured by sensors. Nevertheless, developing an adequately effective estimation scheme for soft robots is not straightforward. First, it requires a mathematical model; modeling of soft robots is analytically demanding due to their complex dynamics. Second, it should perform multimodal sensing for both internal and external variables, with minimal sensors, and finally, it must be robust against sensor faults. In this article, we propose a recurrent neural network-based adaptive unscented Kalman filter (RNN-AUKF) architecture to estimate the proprioceptive state and exteroceptive unknown input of a pneumatic-based soft finger. To address the challenge in modeling soft robots, we adopt a data-driven approach using RNNs. Then, we interconnect the AUKF with an unknown input estimator to perform multimodal sensing using a single embedded flex sensor. We also prove mathematically that the estimation error is bounded with respect to sensor degradation (noise and drift). Experimental results show that the RNN-AUKF achieves a better overall performance in terms of accuracy and robustness against the benchmark method. The proposed scheme is also extended to a multifinger soft gripper and is robust against out-of-distribution sensor dynamics. The outcomes of this research have immense potentials in realizing a robust multimodal indirect sensing in soft robots.