Single-cell sequencing and multiple machine learning algorithms to identify key T-cell differentiation gene for progression of NAFLD cirrhosis to hepatocellular carcinoma.

Introduction: Hepatocellular carcinoma (HCC), which is closely associated with chronicinflammation, is the most common liver cancer and primarily involves dysregulated immune responses in the precancerous microenvironment. Currently, most studies have been limited to HCC incidence. However, the immunopathogenic mechanisms underlying precancerous lesions remain unknown. Methods: We obtained single-cell sequencing data (GSE136103) from two nonalcoholic fatty liver disease (NAFLD) cirrhosis samples and five healthy samples. Using pseudo-time analysis, we systematically identified five different T-cell differentiation states. Ten machine-learning algorithms were used in 81 combinations to integrate the frameworks and establish the best T-cell differentiation-related prognostic signature in a multi-cohort bulk transcriptome analysis. Results: LDHA was considered a core gene, and the results were validated using multiple external datasets. In addition, we validated LDHA expression using immunohistochemistry and flow cytometry. Conclusion: LDHA is a crucial marker gene in T cells for the progression of NAFLD cirrhosis to HCC.

Direction-of-Arrival Estimation via Sparse Bayesian Learning Exploiting Hierarchical Priors with Low Complexity.

For direction-of-arrival (DOA) estimation problems in a sparse domain, sparse Bayesian learning (SBL) is highly favored by researchers owing to its excellent estimation performance. However, traditional SBL-based methods always assign Gaussian priors to parameters to be solved, leading to moderate sparse signal recovery (SSR) effects. The reason is Gaussian priors play a similar role to l2 regularization in sparsity constraint. Therefore, numerous methods are developed by adopting hierarchical priors that are used to perform better than Gaussian priors. However, these methods are in straitened circumstances when multiple measurement vector (MMV) data are adopted. On this basis, a block-sparse SBL method (named BSBL) is developed to handle DOA estimation problems in MMV models. The novelty of BSBL is the combination of hierarchical priors and block-sparse model originating from MMV data. Therefore, on the one hand, BSBL transfers the MMV model to a block-sparse model by vectorization so that Bayesian learning is directly performed, regardless of the prior independent assumption of different measurement vectors and the inconvenience caused by the solution of matrix form. On the other hand, BSBL inherited the advantage of hierarchical priors for better SSR ability. Despite the benefit, BSBL still has the disadvantage of relatively large computation complexity caused by high dimensional matrix operations. In view of this, two operations are implemented for low complexity. One is reducing the matrix dimension of BSBL by approximation, generating a method named BSBL-APPR, and the other is embedding the generalized approximate message passing (GAMB) technique into BSBL so as to decompose matrix operations into vector or scale operations, named BSBL-GAMP. Moreover, BSBL is able to suppress temporal correlation and handle wideband sources easily. Extensive simulation results are presented to prove the superiority of BSBL over other state-of-the-art algorithms.

Visualized detection of water by modified metal organic framework-199 and its portable test paper with reversible color change.

Herein, we fabricate a melamine modified metal organic framework-199 composite (MOF-199@melamine), of which the structure is affected by the dynamics of the guest H2O molecule with significant color change. It realizes the visualized quantitative detection of water in a variety of organic solvents within 30 s. Moreover, DMF restored the original structure by replacing H2O molecules, realizing the regeneration of the materials. On this basis, PTFE-MOF-199@melamine test paper is developed to portably detect water content in organic solvents (maximum 0 %-98 % (v/v) water content) and ambient relative humidity (11-85 %). The test paper can be recycled four times with a regeneration rate higher than 90 %. The results are expected to solve the problems of existed electrochemical or fluorescence strategy such as the complicated operation process and signal output/reading system.

Graphene oxide dispersed mesoporous ZIF-8-encapsulated laccase for removal of toluidine blue with multiple enhanced stability.

The extensive use and discharge of toluidine blue have caused serious problems to the water environment. As a green biocatalyst, laccase has the ability to decolorize the dyes, but it is limited by poor reusability and low stability. Metal-organic frameworks (MOFs) are a good platform for enzyme immobilization. However, due to the weak dispersion of MOFs, the enzyme activity is inevitably inhibited. Herein, we proposed to use graphene oxide (GO) as the dispersion medium of mesoporous ZIF-8 to construct MZIF-8/GO bi-carrier for laccase (FL) immobilization. On account of the narrower bandgap energy of FL@MZIF-8/GO (4.07 eV) than that of FL@MZIF-8 (4.69 eV), electron transport was enhanced which later increased the catalytic activity of the immobilized enzyme. Meanwhile, the improved hydrophilicity characterized by contact angle and full infiltration time further promoted the efficiency of the enzymatic reaction. Benefiting from such regulatory effects of GO, the composite showed excellent storage stability and reusability, as well as multifaceted enhancements including pH, thermal, and solvent adaptation. On the basis of the characterized synergistic effect of adsorption and degradation, FL@MZIF-8/GO was successfully applied to the degradation of toluidine blue (TB) with a removal rate of 94.8%. Even in actual treated wastewater, the highest removal rate still reached more than 80%. Based on the inner mechanism analysis and the universality study, this material is expected to be widely used in the degradation of pollutants in real water under complex environmental conditions.

Esophageal cancer cell-derived small extracellular vesicles decrease circulating Tfh/Tfr via sEV-PDL1 to promote immunosuppression.

Esophageal cancer (EC) is a deadly malignancy. Small extracellular vesicles (sEVs) with programmed death ligand 1 (sEV-PDL1) induce immune escape to promote tumor progression. Furthermore, the imbalance between circulating follicular helper T (Tfh) and circulating follicular regulatory T (Tfr) cells is related to the progression of many malignant tumors. However, the role of the EC-derived sEV-PDL1 in circulating Tfh/Tfr is unknown. Circulating Tfh and Tfr cells were detected by flow cytometry. sEVs were isolated through differential centrifugation and cultured for cell expansion assays. Naïve CD4+ T cells were isolated, stimulated, and cultured with sEVs to evaluate the frequencies, phenotypes, and functions of Tfh and Tfr cells. The proportion of circulating Tfh in patients with EC was lower than that in healthy donors (HDs), whereas that of circulating Tfr was higher. The EC group showed significantly lower circulating Tfh/Tfr and a higher level of sEV-PDL1 than HDs. Notably, sEV-PDL1 was negatively correlated with circulating Tfh/Tfr in the EC group. In vitro assays, sEV-PDL1 inhibited Tfh expansion, enhanced the cytotoxic T lymphocyte-associated antigen 4+ (CTLA4+) Tfh cell percentage, decreased the levels of interleukin (IL)-21 and interferon-γ, and increased IL-10. sEV-PDL1 promoted the expansion and immunosuppressive functions of circulating Tfr; the increased percentages of CTLA4+ Tfr and inducible T cell co-stimulator+ Tfr were accompanied with high IL-10. However, applying an anti-PDL1 antibody significantly reversed this. Our results suggest a novel mechanism of sEV-PDL1-mediated immunosuppression in EC. Inhibiting sEV-PDL1 to restore circulating Tfh/Tfr balance provides a novel therapeutic approach for EC.

Role of exosomes in prostate cancer bone metastasis.

Bone is a preferred metastatic site of prostate cancer (PCa), and most patients with PCa metastases develop osteogenic bone metastasis, which manifests as disturbed bone structure and poor bone quality. However, the underlying mechanisms of PCa bone metastasis remain unclear. In recent years, increasing evidence has implicated extracellular vesicles, especially exosomes, in PCa bone metastasis. Exosomes are 30-150 nm in diameter, enclosing a cargo of biomolecules, such as DNA, RNA, and proteins. Exosomes play a functional role in intercellular communication, modulate the functions of recipient cells, and potentially modulate bone microenvironment changes, thereby influencing the development of PCa bone metastasis. This review summarizes the involvement of exosomes in the imbalance between bone resorption and formation, and establishing a pre-metastatic niche in bone marrow, as well as potential clinical applications of exosomes in therapeutic strategies for treating patients with advanced PCa with bone metastasis.

Laccase encapsulation immobilized in mesoporous ZIF-8 for enhancement bisphenol A degradation.

Endocrine disruptors (EDCs) such as bisphenol A (BPA) have many adverse effects on environment and human health. Laccase encapsulation immobilized in mesoporous ZIF-8 was prepared for efficient degradation of BPA. The ZIF-8 (PA) with highly ordered mesopores was synthesized using trimethylacetic acid (PA) as a template agent. On account of the improvement of skeletal stability by cross-linking agent glutaraldehyde, ZIF-8 (PA) realized laccase (FL) immobilization within the mesopores through encapsulation strategy. By replacing the template agent, the effect of pore size on the composite activity and immobilization efficiency by SEM characterization and kinetic analysis were investigated. Based on the physical protection of ZIF-8(PA) on laccase, as well as electrostatic interactions between substances and changes in surface functional groups (e.g. -OH, etc.), multifaceted enhancement including activity, stability, storability were engendered. FL@ZIF-8(PA) could maintain high activity in complex systems at pH 3-11, 10-70 °C or in organic solvent containing system, which exhibited an obvious improvement compared to free laccase and other reported immobilized laccase. Combined with TGA, FT-IR and Zeta potential analysis, the intrinsic mechanism was elaborated in detail. On this basis, FL@ZIF-8(PA) achieved efficient removal of BPA even under adverse conditions (removal rates all above 55% and up to 90.28%), and was suitable for a wide range of initial BPA concentrations. Combined with the DFT calculations on the adsorption energy and differential charge, the mesoporous could not only improve the enrichment performance of BPA on ZIFs, but also enhance the interaction stability. Finally, FL@ZIF-8(PA) was successfully applied to the degradation of BPA in coal industry wastewater. This work provides a new and ultra-high performances material for the organic pollution treatment in wastewater.

SGOL2 promotes prostate cancer progression by inhibiting RAB1A ubiquitination.

Prostate cancer is the most prevalent genitourinary malignant cancer in men worldwide. Patients with prostate cancer who progress to castration-resistant prostate cancer (CRPC) or metastatic CRPC have significantly poorer survival. Advanced prostate cancer is a clinical challenge due to the lack of effective treatment strategies. In the field of oncology, SGOL2 was an emerging and differentially expressed molecule, which enhanced the proliferation of cell populations in vitro in our studies. Mass spectrum and Co-IP validated the interaction of SGOL2 and RAB1A in a protein-protein manner. We further investigated the role of SGOL2 in the regulatory mechanism of RAB1A in prostate cancer cell lines. Furthermore, SGOL2 regulated RAB1A expression by inhibiting its ubiquitination. Rescue Experiments demonstrated that SGOL2 promoted prostate cancer cell proliferation and migration by upregulating RAB1A expression. Finally, we found that SGOL2 and RAB1A may regulate the tumor microenvironment (TME) in prostate cancer. In conclusion, our findings concluded that SGOL2 stabilized RAB1A expression to promote prostate cancer development. Both of them were of great importance in TME modulation.

Water-stable metal organic framework-199@polyaniline with high-performance removal of copper II.

Metal organic frameworks (MOFs)-based adsorbents for copper ion (Cu2+) generally have the disadvantages of instability in water, low adsorption capacity, and selectivity. Aimed at such problems, we fabricated MOF-199 coated with polyaniline (MOF-199@PANI, core@shell) composite for specific adsorption of Cu2+ in water efficiently. Combined with the characterization by SEM, XRD, and FT-IR, the comprehensively excellent performance probably derived from porous structures of MOF-199, as well as the complexation between Cu2+ and the N atoms of imine moieties in PANI. In addition, the coating process by PANI perfectly protected the MOF skeleton. The isothermal data fitted well to Langmuir isotherm model, of which the calculated adsorption capacity reached 7831.34 mg/g. It was one or two orders of magnitude higher than some other new absorbent for Cu2+ including some carbon-based or organic adsorbents. On the basis of the optimization including pH value, temperature, and ratio of raw materials, the fabricated composite has realized the removal of the spiked Cu2+ in actual fresh water and industrial wastewater samples.

Deterministic Approach to Achieve Full-Polarization Cloak.

Achieving full-polarization (σ) invisibility on an arbitrary three-dimensional (3D) platform is a long-held knotty issue yet extremely promising in real-world stealth applications. However, state-of-the-art invisibility cloaks typically work under a specific polarization because the anisotropy and orientation-selective resonant nature of artificial materials made the σ-immune operation elusive and terribly challenging. Here, we report a deterministic approach to engineer a metasurface skin cloak working under an arbitrary polarization state by theoretically synergizing two cloaking phase patterns required, respectively, at spin-up (σ+) and spin-down (σ-) states. Therein, the wavefront of any light impinging on the cloak can be well preserved since it is a superposition of σ+ and σ- wave. To demonstrate the effectiveness and applicability, several proof-of-concept metasurface cloaks are designed to wrap over a 3D triangle platform at microwave frequency. Results show that our cloaks are essentially capable of restoring the amplitude and phase of reflected beams as if light was incident on a flat mirror or an arbitrarily predesigned shape under full polarization states with a desirable bandwidth of ~17.9%, conceiving or deceiving an arbitrary object placed inside. Our approach, deterministic and robust in terms of accurate theoretical design, reconciles the milestone dilemma in stealth discipline and opens up an avenue for the extreme capability of ultrathin 3D cloaking of an arbitrary shape, paving up the road for real-world applications.