The role of basic leucine zipper transcription factor E4BP4 in cancer: a review and update.

Mutations in the genes of tumor cells and the disorder of immune microenvironment are the main factors of tumor development. The sensitivity of tumor cells to chemotherapy drugs affect the treatment of tumor. Nuclear transcription factor E4BP4 is dysregulated in a variety of malignant tumors. It can suppress the transcription of NFKBIA, RASSF8, SOSTDC1, FOXO-induced genes (TRAIL, FAS, GADD45a and GADD45b) and Hepcidin, up-regulate RCAN1-1 and PRNP, activate mTOR and p38 in cancer cells. Also, E4BP4 can regulate tumor immune microenvironment. TGFb1/Smad3/E4BP4/ IFNγ axis in NK cells plays an important role in antitumor immunotherapy. Over expression of E4BP4 inhibited the development of Th17 cells by directly binding to the RORγt promoter. Moreover, recent studies have shown that E4BP4 inhibited the expression of multidrug resistance genes. In this review, we summarize the molecular mechanism of E4BP4 in cancer cellular process, the effects of E4BP4 in cancer immunotherapy and antitumor drug resistance, to provide theoretical basis for tumor treatment strategies targeting E4BP4.

Engineered Saccharomyces cerevisiae harbors xylose isomerase and xylose transporter improves co-fermentation of xylose and glucose for ethanol production.

Saccharomyces cerevisiae cannot assimilate xylose, second to glucose derived from lignocellulosic biomass. Here, the engineered S. cerevisiae strains INVSc-XI and INVSc-XI/XT were constructed using xylA and Xltr1p to co-utilize xylose and glucose, achieving economic viability and sustainable production of fuels. The xylose utilization rate of INVSc-XI/XT was 2.3-fold higher than that of INVSc-XI, indicating that overexpressing Xltr1p could further enhance xylose utilization. In mixed sugar media, a small amount of glucose enhanced the consumption of xylose by INVSc-XI/XT. Transcriptome analysis showed that glucose increased the upregulation of acetate of coenzyme A synthetase (ACS), alcohol dehydrogenase (ADH), and transketolase (TKL) gene expression in INVSc-XI/XT, further promoting xylose utilization and ethanol yield. The highest ethanol titer of 2.91 g/L with a yield of 0.29 g/g at 96 h by INVSc-XI/XT was 56.9% and 63.0% of the theoretical ethanol yield from glucose and xylose, respectively. These results showed overexpression of xylA and Xltr1p is a promising strategy for improving xylose and glucose conversion to ethanol. Although the ability of strain INVSc-XI/XT to produce ethanol was not very satisfactory, glucose was discovered to influence xylose utilization in strain INVSc-XI/XT. Altering the glucose concentration is a promising strategy to improve the xylose and glucose co-utilization.

INVSc-XI and INVSc-XI/XT strains were newly constructed to utilize xylose and glucose.XylA, in combination with xylose transporter Xltr1p, enhances xylose consumption.A small amount of glucose enhanced xylose utilization in INVSc-XI/XT strain.The expression of ACS, ADH, and TKL genes is upregulated in the media containing mixed sugars.The highest ethanol yield of 0.29 g/g was produced in a 2-L scale-up fermenter.

Metal-Organic Framework-Mediated Synergistic Hypoxia-Activated Chemo-Immunotherapy Induced by High Intensity Focused Ultrasound for Enhanced Cancer Theranostics.

High intensity focused ultrasound (HIFU) has attracted considerable attention as a noninvasive, efficient, and economic therapeutic modality for solid tumors. However, HIFU surgery has its intrinsic limitation in completely ablating tumors, leading to residual tumor tissue. Furthermore, the severely hypoxic environment ensuring after surgery can exacerbate the unrestricted proliferation and metabolism of residual tumor cells, leading to tumor recurrence and metastasis. To address these limitations, a versatile HIFU-specific metal-organic framework nanosystem (called ADMOFs) is developed by coordinating hypoxia-activated prodrug AQ4N, Mn2+ , and DOX based on the postoperative response to changes in the tumor microenvironment. ADMOFs loaded with AQ4N/Mn2+ exhibited remarkable tumor-targeting behavior in vivo and enhanced photoacoustic/magnetic resonance imaging effects, enabling more accurate guidance for HIFU surgery. After surgery, the ADMOFs exploited the severely hypoxic tumor environment induced by HIFU, overcoming hypoxia-associated drug resistance, and inducing immunogenic cell death. Finally, it effectively inhibited tumor growth and eliminated lung metastasis. Transcriptome studies revealed that this strategy significantly up-regulated genes involved in apoptosis, cell cycle, and HIF-1 signaling pathway while downregulating genes related to tumor proliferation and metastasis. These findings suggest that combining hypoxia-activated chemo-immunotherapy with HIFU is a promising strategy for enhancing cancer theranostics.

Stationary Charge Radiation in Anisotropic Photonic Time Crystals.

Time metamaterials offer a great potential for wave manipulation, drawing increasing attention in recent years. Here, we explore the exotic wave dynamics of an anisotropic photonic time crystal (APTC) formed by an anisotropic medium whose optical properties are uniformly and periodically changed in time. Based on a temporal transfer matrix formalism, we show that a stationary charge embedded in an APTC emits radiation, in contrast to the case of isotropic photonic time crystals, and its distribution in momentum space is controlled by the APTC band structure. Our approach extends the functionalities of time metamaterials, offering new opportunities for radiation generation and control, with implications for both classical and quantum applications.

Effective biodegradation of chlorophenols, sulfonamides, and their mixtures by bacterial laccase immobilized on chitin.

Coexisting multi-pollutants like sulfonamides (SAs) and chlorophenols (CPs) in the ecological environment pose a potential risk to living organisms. The development of a strategy for the effective removal of multiple pollutants has become an urgent need. Herein, we systematically investigated the potential of immobilized bacterial laccase to remove chlorophenols (CPs), sulfonamides (SAs), and their mixtures. Laccase from Bacillus pumilus ZB1 was efficiently immobilized on chitin and its thermal stability, pH stability, and affinity to substrates were improved. Reusability assessment showed the immobilized laccase retained 75.5% of its initial activity after five cycles. The removal efficiency of CPs and SAs by immobilized laccase was significantly improved compared with that of free laccase. In particular, the removal of 2,4-dichlorophenol and 2,4,6-trichlorophenol reached 96.9% and 89.3% respectively within 8 h. The immobilized laccase could remove 63.70% of 2,4-dichlorophenol after four cycles. The degradation pathways of 2,4-dichlorophenol and sulfamethazine were proposed via LC/MS analysis. When the co-pollutants containing 2,4,6-trichlorophenol and sulfamethoxazole, immobilized laccase showed 100% removal of 2,4,6-trichlorophenol and 38.71% removal of sulfamethoxazole simultaneously. Cytotoxicity and phytotoxicity tests indicated that immobilized laccase can alleviate the toxicity of co-pollutants. The results demonstrate that chitin-based laccase immobilization can be an effective strategy for the removal of SAs, CPs, and their co-pollutants.

Mechanism of transforming growth factor-ß1 induce renal fibrosis based on transcriptome sequencing analysis. / åŸºäºŽè½¬å½•ç»„æµ‹åºåˆ†æžè½¬åŒ–ç”Ÿé•¿å› å­-ß1诱导肾纤维化机制.

OBJECTIVES: To explore the mechanism of transforming growth factor-ß1 (TGF-ß1) induce renal fibrosis. METHODS: Renal fibroblast NRK-49F cells treated with and without TGF-ß1 were subjected to RNA-seq analysis. DESeq2 was used for analysis. Differentially expressed genes were screened with the criteria of false discovery rate<0.05 and l o g 2 F C >1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for differentially expressed genes. Genes encoding transcription factors were further screened for differential expression genes. Then, the expression of these genes during renal fibrosis was verified using unilateral ureteral obstruction (UUO)-induced mouse renal fibrosis model and a public gene expression dataset (GSE104954). RESULTS: After TGF-ß1 treatment for 6, 12 and 24 h, 552, 1209 and 1028 differentially expressed genes were identified, respectively. GO analysis indicated that these genes were significantly enriched in development, cell death, and cell migration. KEGG pathway analysis showed that in the early stage of TGF-ß1 induction (TGF-ß1 treatment for 6 h), the changes in Hippo, TGF-ß and Wnt signaling pathways were observed, while in the late stage of TGF-ß1 induction (TGF-ß1 treatment for 24 h), the changes of extracellular matrix-receptor interaction, focal adhesion and adherens junction were mainly enriched. Among the 291 up-regulated differentially expressed genes treated with TGF-ß1 for 6 h, 13 genes (Snai1, Irf8, Bhlhe40, Junb, Arid5a, Vdr, Lef1, Ahr, Foxo1, Myc, Tcf7, Foxc2, Glis1) encoded transcription factors. Validation in a cell model showed that TGF-ß1 induced expression of 9 transcription factors (encoded by Snai1, Irf8, Bhlhe40, Junb, Arid5a, Vdr, Lef1, Myc, Tcf7), while the expression levels of the other 4 genes did not significantly change after TGF-ß1 treatment. Validation results in UUO-induced mouse renal fibrosis model showed that Snai1, Irf8, Bhlhe40, Junb, Arid5a, Myc and Tcf7 were up-regulated after UUO, Vdr was down-regulated and there was no significant change in Lef1. Validation based on the GSE104954 dataset showed that IRF8 was significantly overexpressed in the renal tubulointerstitium of patients with diabetic nephropathy or IgA nephropathy, MYC was highly expressed in diabetic nephropathy, and the expressions of the other 7 genes were not significantly different compared with the control group. CONCLUSIONS: TGF-ß1 induces differentially expressed genes in renal fibroblasts, among which Irf8 and Myc were identified as potential targets of chronic kidney disease and renal fibrosis.

Nonreciprocity and Faraday Rotation at Time Interfaces.

Nonreciprocity is critically important in modern wave technologies, yet its general principles and practical implementations continue to raise intense research interest, in particular in the context of broken reciprocity based on spatiotemporal modulation. Abrupt changes in time of the electromagnetic properties of a material have also been shown to replace spatial boundaries, supporting highly unusual wave-matter interactions in so-called time metamaterials. Here, we introduce nonreciprocity for temporal boundaries, demonstrating Faraday polarization rotation in a magnetoplasma with material properties abruptly switched in time. Our findings open new opportunities for time metamaterials, yielding new avenues for nonreciprocity with broad applicability for wave engineering.

Assembling Alkaline-Responsive Chitosan@Giant Liposomes through an Ultrasound-Integrated Microfluidic Approach.

This paper presents the fabrication of an alkaline-responsive drug carrier, chitosan@giant liposome (CS-GL), by using an ultrasound-integrated microfluidic approach. On the microfluidic chip, water/oil/water droplets are first prepared and then move through an area of ultrasonic radiation to improve the regional saturation of organic solvent and accelerate its removal. At the same time, phospholipid molecules in the oil phase of the droplets are efficiently self-assembled into giant liposomes (GLs). Subsequently, microfluidic channels combined with an up-down separated structure can help in the fabrication and purification of the GLs. Due to the electrostatic interaction between the amino group of chitosan and the phosphate group of phospholipids, the GLs and chitosan are assembled into CS-GLs. The change of ζ potential after this operation indicates that chitosan is coated on the surface of GLs. The formed CS-GLs are monodispersed with a 54.1 ± 0.7 µm diameter and high drug encapsulation efficiency (∼96%), and the structural integrity can be kept without leakage of contents for more than a week in an acid medium (pH = 1.2). When this structure is placed in an aqueous solution of pH = 7.8, chitosan precipitates gradually and detaches from the GL, causing its rupture. The drug encapsulated in a single CS-GL can be rapidly released within 4 s, and 99.6% of the CS-GL carriers can complete the release within 10 min.

Construction of lncRNA-miRNA-mRNA network based on ceRNA mechanism reveals the function of lncRNA in the pathogenesis of gout.

OBJECTIVE: To identify differentially expressed lncRNA, miRNA, and mRNA during the pathogenesis of gout, explore the ceRNA network regulatory mechanism of gout, and seek potential therapeutic targets. METHOD: First, gout-related chips were retrieved by GEO database. Then, the analysis of differentially expressed lncRNAs and mRNAs was conducted by R language and other software. Besides, miRNA and its regulated mRNA were predicted based on public databases, the intersection of differentially expressed mRNA and predicated mRNA was taken, and the lncRNA-miRNA-mRNA regulatory relationships were obtained to construct the ceRNA regulatory network. Subsequently, hub genes were screened by the STRING database and Cytoscape software. Then the DAVID database was used to illustrate the gene functions and related pathways of hub genes and to mine key ceRNA networks. RESULTS: Three hundred and eighty-eight lncRNAs and 758 mRNAs were identified with significant differential expression in gout patient, which regulates hub genes in the ceRNA network, such as JUN, FOS, PTGS2, NR4A2, and TNFAIP3. In the ceRNA network, lncRNA competes with mRNA for miRNA, thus affecting the IL-17 signaling pathway, TNF signaling pathway, Oxytocin signaling pathway, and NF-κB signaling pathway through regulating the cell's response to chemical stress. The research indicates that five miRNAs (miR-429, miR-137, miR-139-5p, miR-217, miR-23b-3p) and five lncRNAs (SNHG1, FAM182A, SPAG5-AS1, HNF1A-AS1, UCA1) play an important role in the formation and development of gout. CONCLUSION: The interaction in the ceRNA network can affect the formation and development of gout by regulating the body's inflammatory response as well as proliferation, differentiation, and apoptosis of chondrocytes and osteoclasts. The identification of potential therapeutic targets and signaling pathways through ceRNA network can provide a reference for further research on the pathogenesis of gout.

Efficient removal of azo dyes by Enterococcus faecalis R1107 and its application in simulated textile effluent treatment.

This study aimed to exploit the potential of Enterococcus faecalis R1107 in the bioremediation of azo dyes. The maximal decolorization of Congo Red (CR), Reactive Black 5 (RB5), and Direct Black 38 (DB38) were 90.17%, 96.82%, and 81.95%, respectively, with the bacterial treatment for 48 h. 65.57% of CR and 72.64% of RB5 could be decolorized by E. faecalis R1107 within 48 h when the concentration of azo dyes increased up to 1000 mg/L. FTIR analysis confirmed that E. faecalis R1107 could effectively break down the chemical structures of three azo dyes. E. faecalis R1107 alleviated the phytotoxicity of azo dyes and improved seed germination, which contributed to the increase in the lengths of roots, stems, and leaves of Vigna radiata seedlings. Transcriptomic analysis suggested that the gene regulatory networks in E. faecalis R1107 synergistically improved the degradation and detoxification of RB5, including the major metabolic pathways, the secondary metabolism, the transport system, the amino acid metabolic pathways, and the signal transduction systems. Simulated textile effluent (STE) was used to mimic real textile effluent to evaluate the bioremediation potential of E. faecalis R1107, and 72.79% STE can be decolorized after E. faecalis R1107 treatment for 48 h. In summary, our study demonstrated that E. faecalis R1107 might be well suitable for potential applications in the bioremediation of textile effluent.

Tunable Chiral Optics in All-Solid-Phase Reconfigurable Dielectric Nanostructures.

Subwavelength nanostructures with tunable compositions and geometries show favorable optical functionalities for the implementation of nanophotonic systems. Precise and versatile control of structural configurations on solid substrates is essential for their applications in on-chip devices. Here, we report all-solid-phase reconfigurable chiral nanostructures with silicon nanoparticles and nanowires as the building blocks in which the configuration and chiroptical response can be tailored on-demand by dynamic manipulation of the silicon nanoparticle. We reveal that the optical chirality originates from the handedness-dependent coupling between optical resonances of the silicon nanoparticle and the silicon nanowire via numerical simulations and coupled-mode theory analysis. Furthermore, the coexisting electric and magnetic resonances support strong enhancement of optical near-field chirality, which enables label-free enantiodiscrimination of biomolecules in single nanostructures. Our results not only provide insight into the design of functional high-index materials but also bring new strategies to develop adaptive devices for photonic and electronic applications.

Temporal Parity-Time Symmetry for Extreme Energy Transformations.

Temporal interfaces introduced by abrupt switching of the constitutive parameters of unbounded media enable unusual wave phenomena. So far, their explorations have been mostly limited to lossless media. Yet, non-Hermitian phenomena leveraging material loss and gain, and their balanced combination in parity-time (PT)-symmetric systems, have been opening new vistas in photonics. Here, we unveil the role that temporal interfaces offer in non-Hermitian physics, introducing the dual of PT symmetry for temporal boundaries. Our findings reveal unexplored interference mechanisms enabling extreme energy manipulation, and open new scenarios for time-switched metamaterials, connecting them with the broad opportunities offered by non-Hermitian phenomena.

Gain-Free Parity-Time Symmetry for Evanescent Fields.

Parity-time (PT) symmetry, satisfied when a system commutes under combined parity and time-reversal operations, enables extreme optical responses in non-Hermitian systems with balanced distributions of gain and loss. In this Letter, we propose a different path for PT symmetry utilizing the evanescent field excitation of anti-PT-symmetric structures, which anticommute with the PT operator and do not necessarily require gain. Beyond offering a robust platform to explore PT symmetry, our study showcases an important link between non-Hermitian physics and near-field interactions, with implications in nanophotonics, plasmonics, and acoustics for nanoimaging, sensing, and communications.

Extreme Nonreciprocal Near-Field Thermal Radiation via Floquet Photonics.

By using Floquet driving protocols and interlacing them with a judicious reservoir emission engineering, we achieve extreme nonreciprocal thermal radiation. We show that the latter is rooted in an interplay between a direct radiation process occurring due to temperature bias between two thermal baths and the modulation process that is responsible for pumped radiation heat. Our theoretical results are confirmed via time-domain simulations with photonic and rf circuits.

Chemically induced oxidative stress improved bacterial laccase-mediated degradation and detoxification of the synthetic dyes.

To alleviate the risk of textile effluent, the development of highly effective bioremediation strategies for synthetic dye removal is needed. Herein, we aimed to assess whether intensified bioactivity of Bacillus pumilus ZB1 by oxidative stress could improve the removal of textile dyes. Methyl methanesulfonate (MMS) induced oxidative stress significantly promoted laccase expression of B. pumilus ZB1. Both the level of hydrogen dioxide and superoxide anion showed a significant positive correlation with laccase activity (RSQ = 0.963 and 0.916, respectively) along with the change of MMS concentration. The regulation of laccase expression was closely related to oxidative stress. The overexpressed laccase in the supernatant improved the decolorization of synthetic dyes (16.43% for Congo Red, 54.05% for Crystal Violet, and 41.61% for Reactive Blue 4). Laccase was subsequently expressed in E. coli. Investigation of the potential of bacterial laccase in dye remediation using Congo Red showed that an effective degradation of azo dye could be achieved with laccase treatment. Laccase remediation alleviated the cytotoxicity of Congo Red to human hepatocytes. In silico study identified eight amino acid residues of laccase involved in binding with Congo Red. Overall, regulation of oxidative stress towards bacterium can be used as a promising approach for the improvement of bacterial bioactivity in synthetic dye remediation.

Effect of Rhodococcus sp. pretreatment on cellulose hydrolysis of corn stalk.

Pretreatment can improve the hydrolysis efficiency of cellulose, in which biological pretreatment plays an important role. In the present study, we uncovered that Rhodococcus has the ability of lignin degradation, which can decompose lignin and serve as a carbon source to meet the needs of its own growth. We used Rhodococcus to pretreat the corn stalks and evaluate the effect on cellulose hydrolysis. The concentration of reducing sugar produced by the hydrolysis of corn stalk after pretreatment of Rhodococcus is 2.95 g/L. SEM imaging showed that Rhodococcus pretreatment resulted the surface of corn stalk to be no longer complete, some lamellar structures fall off, and leave obvious traces, and obvious delamination was found at the edge of the fault. AFM imaging showed that the pretreatment changed the lignin structure of the corn stalk material surface, resulting in a higher surface roughness of 9.37. These results indicated that Rhodococcus pretreatment can improve the saccharification efficiency of cellulose by removing lignin and increasing the surface roughness of the material.

Icariin regulates miR-23a-3p-mediated osteogenic differentiation of BMSCs via BMP-2/Smad5/Runx2 and WNT/ß-catenin pathways in osteonecrosis of the femoral head.

Icariin is commonly used for the clinical treatment of osteonecrosis of the femoral head (ONFH). miR-23a-3p plays a vital role in regulating the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). The present study aimed to investigate the roles of icariin and miR-23a-3p in the osteogenic differentiation of BMSCs and an ONFH model. BMSCs were isolated and cultured in vitro using icariin-containing serum at various concentrations, and BMSCs were also transfected with a miR-23a inhibitor. The alkaline phosphatase (ALP) activity and cell viability as well as BMP-2/Smad5/Runx2 and WNT/ß-catenin pathway-related mRNA and protein expression were measured in BMSCs. Additionally, a dual-luciferase reporter assay and pathway inhibitors were used to verify the relationship of icariin treatment/miR-23a and the above pathways. An ONFH rat model was established in vivo, and a 28-day gavage treatment and lentivirus transfection of miR-23a-3p inhibitor were performed. Then, bone biochemical markers (ELISA kits) in serum, femoral head (HE staining and Digital Radiography, DR) and the above pathway-related proteins were detected. Our results revealed that icariin treatment/miR-23a knockdown promoted BMSC viability and osteogenic differentiation as well as increased the mRNA and protein expression of BMP-2, BMP-4, Runx2, p-Smad5, Wnt1 and ß-catenin in BMSCs and ONFH model rats. In addition, icariin treatment/miR-23a knockdown increased bone biochemical markers (ACP-5, BAP, NTXI, CTXI and OC) and improved ONFH in ONFH model rats. In addition, a dual-luciferase reporter assay verified that Runx2 was a direct target of miR-23a-3p. These data indicated that icariin promotes BMSC viability and osteogenic differentiation as well as improves ONFH by decreasing miR-23a-3p levels and regulating the BMP-2/Smad5/Runx2 and WNT/ß-catenin pathways.

Evolution and Antigenic Drift of Influenza A (H7N9) Viruses, China, 2017-2019.

After a sharp decrease of influenza A(H7N9) virus in China in 2018, highly pathogenic H7N9 viruses re-emerged in 2019. These H7N9 variants exhibited a new predominant subclade and had been cocirculating at a low level in eastern and northeastern China. Several immune escape mutations and antigenic drift were observed in H7N9 variants.

Robust Scattered Fields from Adiabatically Driven Targets around Exceptional Points.

Scattering processes are typically sensitive to the incident wave properties and to interference effects generated via wave-matter interactions with the target. We challenge this general belief in the case of targets that undergo time-periodic modulations encircling quasiadiabatically an exceptional point in a given parameter space. When the scattering dwell time is above a critical value τ_{c}, the scattered field is surprisingly insensitive to the properties of the incoming wave and local operational details of the driving. Instead, it reaches a fixed point attractor that can be controlled by the direction of the driving cycle. For dwell times below τ_{c}, the unusual robustness is abruptly suppressed. Such protocols may become useful tools in control engineering, including the management of thermal and quantum fluctuations.

Virtual Parity-Time Symmetry.

Parity-time (PT) symmetry has recently been opening exciting directions in photonics, yet the required careful balance of loss and gain has been hindering its widespread applicability. Here, we propose a gain-free route to PT symmetry by extending it to complex-frequency excitations that can mimic gain in passive systems. Based on the concept of virtual absorption, extended here to implement also virtual gain, we implement PT symmetry in the complex-frequency plane and realize its landmark effects, such as broken phase transitions, anisotropic transmission resonances, and laser-absorber pairs, in a fully passive, hence inherently stable, system. These results open a path to establish PT symmetry and non-Hermitian physics in passive platforms.