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Although conventional therapeutic approaches demonstrate significant success in treating primary tumors, their efficacy diminishes when addressing distant and metastatic tumors, calling for new technologies to transport and activate the therapeutic agents. Here, a core‐shell UCNP@MOF (upconversion nanoparticle — metal organic framework) nanoagents is constructed for Type I and Type II photodynamic therapy under biocompatible near‐infrared light irradiance (at 808 nm) and utilize their pore loading capacity to further realize synergistic immunotherapy in solid tumors. The Cu2+ to Cu+ reduction at the nodes in the MOFs shell is demonstrated to promote the generation of reactive oxygen species via depletion of overexpressed glutathione (GSH) compounds, while tumor microenvironment‐enriched hydrogen peroxide is found to substantially augment the PDT effects. Importantly, the MOFs pore‐loaded indoleamine 2,3‐dioxygenase (IDO) inhibitor, along with s‐nitroso‐n‐acetylpenicillamine (SNAP), upregulated tumor‐infiltrating lymphocytes and induced prominent immunotherapeutic effects in vivo. This core‐shell UCNP@MOF nanoagents have demonstrated effectiveness against both primary and distant tumors in xenografted tumor models, holding promise for treating solid tumors in metastasis. [ABSTRACT FROM AUTHOR]

In order to develop new feed resources, the aim of this study was to investigate the effects of moisture content, additives, and their interactions on the fermentation quality, aerobic stability, and in vitro digestibility of mixed silage of amaranth and cornmeal. The mass ratios of amaranth and cornmeal were 69:31, 76:24, and 84:16 for adjusting the moisture content of silage to 60% (W1), 65% (W2), and 70% (W3), respectively. The silage treatments included no additives (U), the addition of Lactobacillus plantarum (L), the addition of cellulase (E), and the addition of Lactobacillus plantarum + cellulase (M) mixed reagents. The results revealed that the pH and ammonia nitrogen (NH3-N/TN) ratios were significantly lower in W1 than in W2 and W3 (3.66,19.3 g kg−1 TN vs. 3.70, 3.70, 20.0 kg−1 TN, 25.1 kg−1 TN, p < 0.05). Moreover, dry matter (DM), organic matter (OM), in vitro dry matter digestibility (ivDMD), in vitro organic matter digestibility (ivOMD), and in vitro crude protein digestibility (ivCPD) significantly increased (p < 0.05). Meanwhile, the aerobic stability of mixed silage containing amaranth and cornmeal decreased with increasing water content. The aerobic stability of the L, E, and M treatment groups was improved by 15, 105, and 111 h, respectively, compared with that of the control group at W1. The pH and NH3-N/TN ratios were lower with the addition of E (E and M) than with the absence of E (U and L) (3.73, 20.1 g kg−1 DM vs. 3.64, 22.9 g kg−1 DM, p < 0.05). NDF and ADF were significantly lower with the addition of E than without the addition of E (598 g kg−1 DM, 145 g kg−1 DM vs. 632 g kg−1 DM, 160 g kg−1 DM, p < 0.05). However, CP, ivDMD, ivOMD, and ivCPD were significantly higher (p < 0.05). AA and NH3-N/TN were significantly lower (p < 0.05) with the addition of L (L and M) than without the addition of L (U and E). In conclusion, the best fermentation quality, in vitro digestibility, and aerobic stability of amaranth and cornmeal mixed silage treated with Lactobacillus plantarum + cellulase (M) were achieved at 60% water content. The present study confirmed the potential of amaranth as silage and its potential application for improving feed quality and animal performance. [ABSTRACT FROM AUTHOR]

Simple Summary: Under the shortage of roughage resources in China, Silphium perfoliatum L. (SP) can be an ideal roughage choice for ruminants and has good application prospects. Ensiling is an efficient forage treatment technology for retaining the nutrients and extending the shelf life of forage. At present, there have been no reports on the effects of Lactobacillus plantarum and Lactobacillus buchneri, whether alone or in combination, on Silphium perfoliatum L. silage. Therefore, in this experiment, L. plantarum and L. buchneri were added individually or combined to SP-silage to investigate the effects of different fermentation types of Lactobacilli on the fermentation quality, in vitro digestibility, and aerobic stability of SP-silage. It was found that a mixture of L. plantarum and L. buchneri provided the best silage results. L. buchneri can be used as an additive to improve the aerobic stability of SP-silage. The results of our research provide a certain scientific basis and technical support for obtaining high-quality SP-silage in production. In this experiment, Lactobacillus plantarum and Lactobacillus buchneri were added individually or in combination to Silphium perfoliatum L. (SP) silage to investigate the effects of different fermentation types of lactobacilli on the fermentation quality, in vitro digestibility, and aerobic stability of SP-silage, with a view to providing a certain scientific basis and technical support for obtaining high-quality SP-silage in production. The experiment comprised a non-additive group (control), an L. plantarum group (LP), an L. buchneri group (LB), and an L. plantarum and L. buchneri mixed treatment group (LPLB). Samples were taken after 60 days of fermentation and analyzed for the fermentation quality, in vitro digestibility, and aerobic stability of the SP-silage. The results showed that the addition of LP, LB, and LPLB significantly reduced the pH and proportion of ammonia nitrogen to total nitrogen and significantly increased the lactic acid, in vitro dry matter digestibility, and in vitro crude protein digestibility in the SP-silage (p < 0.05). Compared to the control group, the dry matter and crude protein contents of the LB and LPLB groups were significantly increased, while the neutral detergent fiber and acid detergent fiber contents were significantly reduced (p < 0.05). The SP-silage supplemented with LPLB had the highest dry matter and crude protein contents. The gross and digestible energies of the SP-silage in the LB and LPLB groups were significantly higher than those in the control and LP groups (p < 0.05). The aerobic stability of the SP-silage was significantly reduced by 24.14% in the LP group and increased by 58.62% and 34.48% in the LB and LPLB groups, respectively, compared to the control group (p < 0.05). It was shown that adding a combination of LP and LB resulted in the best fermentation quality, nutritional value, and in vitro digestibility of the SP-silage. LB was effective in improving the aerobic stability of SP-silage. [ABSTRACT FROM AUTHOR]

RhlR plays a key role in the quorum sensing of Pseudomonas aeruginosa. The current structure–activity relationship (SAR) studies of RhlR inhibitors mainly focus on elucidating the functional groups. Based on a systematic review of previous research on RhlR inhibitors, this study aims to establish a systematic, hierarchical screening model for RhlR inhibitors. We initially established a database and utilized principal component analysis (PCA) to categorize the inhibitors into two classes. Based on the training set, pharmacophore models were established to elucidate the structural characteristics of ligands. Subsequently, molecular docking, molecular dynamics simulations, and the calculation of binding free energy and strain energy were performed to validate the crucial interactions between ligands and receptors. Then, the screening criteria for RhlR inhibitors were established hierarchically based on ligand structure characteristics, ligand–receptor interaction, and receptor affinity. Test sets were finally employed to validate the hierarchical virtual screening model by comparing it with the current SAR studies of RhlR inhibitors. The hierarchical screening model was confirmed to possess higher accuracy and a true positive rate, which holds promise for subsequent screening and the discovery of active RhlR inhibitors. [ABSTRACT FROM AUTHOR]

A novel modified polyaspartic acid (PASP/CD) was synthesized from thiocarbazide and polysuccinim-ide. Secondly, the structure of PASP/CD was characterized by infrared spectroscopy (FT1R) and hydrogen nuclear magnetic resonance spectroscopy (NMR). Finally, the corrosion inhibition behavior of PASP/CD on carbon steel was studied by gravimetry, electrochemical method, atomic force microscope (AFM), contact angle and scanning electron microscope and energy spectrum (SEM/EDS) in 0.5 mol/L hydrochloric acid solution. The results show that when PASP/CD is added into hydrochloric acid solution as a mixed corrosion inhibitor, the charge transfer resistance of the system increases significantly. When the concentration of PASP/CD is 80 mg/L, the corrosion inhibition efficiency reaches 91.48%, which is much higher than PASP. Compared with PASP, the corrosion inhibition performance of PASP/CD is less affected by temperature. The figures and roughness data of AFM show that PASP/CD has good corrosion inhibition performance. It is found that the inhibition effect of PASP/CD is due to the physical and chemical adsorption of new functional groups on the steel surface. This work provides technical support for broadening the comprehensive properties of green water treatment agent polyaspartic acid. [ABSTRACT FROM AUTHOR]

Noninvasive sonodynamic therapy (SDT) shows promise for brain glioma treatment due to deep tissue‐penetrating capabilities (>10 cm) of ultrasound and high spatial resolutions. Yet, this technique is hindered by inefficient production of reactive oxygen species (ROS), resulting from the hypoxic tumor microenvironment (TME), high level of ROS scavenger glutathione (GSH), and the inability to visualize glioma in vivo for precise treatment management and monitoring in current sonosentizers. To address these challenges, we fabricated a core‐shell heterostructure sonosensitizer (labeled as DFM), in which meso‐tetra (4‐carboxyphenyl) porphine (TCPP) porphyrin metal‐organic frameworks (MOF, PCN‐224(Fe)) serve as a porous shell to contain approved chemotherapeutics sorafenib (SRF) to effectively inhibit GSH synthesis, while NaErF4:Yb@NaLuF4 nanoparticles as the core provide TME‐responsive NIR IIb (≈1500–1800 nm) luminescence at 1525 for precise optical imaging. Coordination of Fe3+ into the macrocycle of TCPP at the MOFs shell is found to, besides triggering ferroptosis, reduce TCPP phosphorescence (23% decrease) and increase the triplet state (T1) oxygen quenching, substantially promoting the singlet oxygen generation (2.6‐fold increase). Furthermore, GSH in TME facilitates the reduction of Fe3+ to Fe2+, thereby eliminating the luminescence quenching of Fe3+ and augmenting the NIR IIb luminescence of Er3+ (5‐fold increase) for nanoagents accumulation imaging in intracranial glioma, realizing dynamical monitoring of SDT processes. Compared to control groups, in vitro and in vivo experiments confirm the effective ROS generation and results in a 6‐fold volume reduction of brain gliomas, reaching a survival rate of 80% at 30 days posttreatment. [ABSTRACT FROM AUTHOR]

α1C-tubulin (TUBA1C) is a member of the α-tubulin family and has served as a potential biomarker in a variety of cancers in many studies. In this study, the gene expression profile of TUBA1C in The Cancer Genome Atlas (TCGA) was extracted for analysis, and the prognostic value of TUBA1C in breast cancer was comprehensively evaluated. The Wilcoxon signed-rank test, Kruskal-Wallis test, and logistic regression analysis were performed to confirm the correlations between TUBA1C expression and the clinical characteristics of breast cancer patients. The effect of TUBA1C expression on the survival of breast cancer patients was assessed by Kaplan-Meier curve, Cox regression analysis, and the Kaplan-Meier plotter (an online database). The TCGA data set was used for the Gene Set Enrichment Analysis (GSEA). The results confirmed that high TUBA1C expression in breast cancer was closely correlated with survival time, survival status, and tumor size. In addition, elevated TUBA1C expression can predict poor overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS). Univariate and multivariate analyses (Cox regression analyses) confirmed that TUBA1C was an independent prognostic factor for the OS of breast cancer patients. The GSEA identified that the high TUBA1C expression phenotype was differentially enriched in cell cycle, basal transcription factor, P53 signaling pathway, pathways in cancer, TOLL-like receptor signaling pathway, and NOD-like receptor signaling pathway. In summary, high messenger RNA (mRNA) expression of TUBA1C is an independent risk factor for poor prognosis of breast cancer. [ABSTRACT FROM AUTHOR]

Dynamic regulation of nanoparticles in a controllable manner has great potential in various areas. Compared to the individual nanoparticles, the assembled nanoparticles exhibit superior properties and functions, which can be applied to achieve desirable performances. Here, a pH‐responsive i‐motif DNA‐mediated strategy to tailor the programmable behaviors of erbium‐based rare‐earth nanoparticles (ErNPs) decorated copper doped metal‐organic framework (CPM) nanohybrids (ECPM) under physiological conditions is reported. Within the acidic tumor microenvironment, the i‐motif DNA strands are able to form quadruplex structures, resulting in the assembly of nanohybrids and selective tumor accumulation, which further amplify the ErNPs downconversion emission (1550 nm) signal for imaging. Meanwhile, the ECPM matrix acts as a near‐infrared (NIR) photon‐activated reactive oxygen species (ROS) amplifier through the singlet oxygen generation of the matrix in combination with its ability of intracellular glutathione depletion upon irradiation. In short, this work displays a classical example of engineering of nanoparticles, which will manifest the importance of developing nanohybrids with structural programmability in biomedical applications. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) have been proven to exert important functions in the various biological processes of human cancers. It has been reported that lncRNA HNF1 homeobox A antisense RNA 1 (HNF1A‐AS1) was abnormally expressed and played a role in the initiation and development of various human cancers. In this study, we confirmed that the expression level of HNF1A‐AS1 was increased in glioma tissues and cells. Knockdown of HNF1A‐AS1 inhibited cell proliferation and promoted cell apoptosis in glioma. Then, we disclosed the downregulation of miR‐363‐3p in glioma tissues and cell lines. The interaction between HNF1A‐AS1 and miR‐363‐3p was identified in glioma cells. Furthermore, an inverse correlation between HNF1A‐AS1 and miR‐363‐3p was observed in glioma tissues. Afterwards, we recognized that MAP2K4 was a direct target of miR‐363‐3p. The expression of MAP2K4 was negatively correlated with miR‐363‐3p while positively related to HNF1A‐AS1 in glioma tissues. We also found the regulatory effect of HNF1A‐AS1 on the MAP2K4‐dependent JNK signaling pathway. All findings indicated that HNF1A‐AS1 induces the upregulation of MAP2K4 to activate the JNK signaling pathway to promote glioma cell growth by acting as a miR‐363‐3p sponge. [ABSTRACT FROM AUTHOR]

The cross‐linking degree (crystallinity) and proton sources of conductors strongly impacts proton‐conducting properties, but the attention is still limited, especially for covalent‐organic frameworks. Here, we prepared a couple of cross‐linking degrees of Schiff‐Based Network by solvothermal (high surface specific area, SNW‐S) and microwave‐assisted (low cross‐linking structure, SNW‐M) strategies, respectively; subsequently, Brønsted acids (BAs)‐entrapped Schiff‐Based Network (SNW) composites as fillers are blended into polyvinyl pyrrolidone/poly(vinylidene fluoride) (PP) blends to form hybrid membranes. Varied crystalline degrees and microstructures of the SNWs are monitored by XRD, FTIR, and nitrogen adsorption, coupled with relevant conduction measurements like water uptake and proton conductivity (PC) for the composites and hybrid membranes. Structurally, under the aid of "acid–base pairs" between amine groups in Schiff‐Based Network and Brønsted acids as proton carriers, the resulting H2SO4‐incorporated SNW‐M with poor cross‐linking displays the high proton conductivity (4.96 × 10−3 S/cm) with an activation energy of 0.13 eV, whereas H2SO4 and H3PO4‐incorporated SNW‐S appear the relatively lower conductivities, imputable to the differences in the cross‐linking degree of Schiff‐Based Network and interactions between proton carriers and active sites in Schiff‐Based Network. Additionally, the hybrid membranes also show σ values in the identical level of the composites, reaching to 8.02 × 10−3 S/cm at 323 K. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most universal and invasive brain tumor among adults. Increasing studies have reported that long noncoding RNAs play vital roles in regulating downstream molecules at the transcriptional or posttranscriptional level in tumor progression. The purpose of the current research was to inquire the modulation mechanism by which homeobox B cluster antisense RNA 1 (HOXB‐AS1) functioned in GBM. Our study first discovered the lifted expression of HOXB‐AS1 and its nearby genes HOXB2 and HOXB3 in GBM and the positive relationship between HOXB‐AS1 and HOXB2 or HOXB3. Loss‐of‐function assays and in vivo study detected that silencing of HOXB‐AS1, HOXB2, or HOXB3 restrained the proliferation and induced the apoptosis in GBM. In addition, mechanism experiments demonstrated that HOXB‐AS1 recruited interleukin enhancer‐binding factor 3 (ILF3) to regulate HOXB2 and HOXB3 expression at the transcriptional level, and HOXB‐AS1 sponged miR‐186‐5p to modulate HOXB2 and HOXB3 expression at posttranscriptional level. Finally, the regulatory mechanism of HOXB‐AS1 in GBM was certified through rescue experiments. Our results indicated that HOXB‐AS1 boost the HOXB2 or HOXB3 expression at the transcriptional and posttranscriptional levels. We detected the HOXB‐AS1‐ILF3‐HOXB2/HOXB3 axis and HOXB‐AS1‐miR‐186‐5p‐HOXB2/HOXB3 axis driving the GBM progression, which might generate more effective diagnostic biomarkers and therapeutic targets for patients with GBM. [ABSTRACT FROM AUTHOR]