miR-182 targeting reprograms tumor-associated macrophages and limits breast cancer progression.

The protumor roles of alternatively activated (M2) tumor-associated macrophages (TAMs) have been well established, and macrophage reprogramming is an important therapeutic goal. However, the mechanisms of TAM polarization remain incompletely understood, and effective strategies for macrophage targeting are lacking. Here, we show that miR-182 in macrophages mediates tumor-induced M2 polarization and can be targeted for therapeutic macrophage reprogramming. Constitutive miR-182 knockout in host mice and conditional knockout in macrophages impair M2-like TAMs and breast tumor development. Targeted depletion of macrophages in mice blocks the effect of miR-182 deficiency in tumor progression while reconstitution of miR-182-expressing macrophages promotes tumor growth. Mechanistically, cancer cells induce miR-182 expression in macrophages by TGFß signaling, and miR-182 directly suppresses TLR4, leading to NFκb inactivation and M2 polarization of TAMs. Importantly, therapeutic delivery of antagomiR-182 with cationized mannan-modified extracellular vesicles effectively targets macrophages, leading to miR-182 inhibition, macrophage reprogramming, and tumor suppression in multiple breast cancer models of mice. Overall, our findings reveal a crucial TGFß/miR-182/TLR4 axis for TAM polarization and provide rationale for RNA-based therapeutics of TAM targeting in cancer.

Sustained Phosphorus Removal and Enrichment through Off-Flow Desorption in a Reservoir of Membrane Capacitive Deionization.

In this study, we used a membrane capacitive deionization device with a reservoir (R-MCDI) to enrich phosphorus (P) from synthetic wastewater. This R-MCDI had two small-volume electrode chambers, and most of the electrolyte was contained in the reservoir, which was circulated along the electrode chambers. Compared with conventional MCDI, R-MCDI exhibited a phosphate removal rate of 0.052 µmol/(cm2·min), approximately double that of MCDI. This was attributed to R-MCDI's utilization of OH- alternative adsorption to remove phosphate from the influent. Noticing that around 73.9% of the removed phosphate was stored in the electrolyte in R-MCDI, we proposed a novel off-flow desorption operation to enrich the removed phosphate in the reservoir. Exciting results from the multicycle experiment (∼8 h) of R-MCDI showed that the PO43--P concentration in the reservoir increased all the way from the initial 152 mg/L to the final 361 mg/L, with the increase in the P charge efficiency from 5.5 to 22.9% and the decrease in the energy consumption from 28.2 to 6.8 kW h/kg P. The P recovery performance of R-MCDI was evaluated by viewing other similar studies, which revealed that R-MCDI in this study achieved superior P enrichment with low energy consumption and that the off-flow desorption proposed here considerably simplified the operation and enabled continuous P enrichment.

lncRNA HITT inhibits metastasis by attenuating Rab5-mediated endocytosis in lung adenocarcinoma.

Endocytosis of cell surface receptors is essential for cell migration and cancer metastasis. Rab5, a small GTPase of the Rab family, is a key regulator of endosome dynamics and thus cell migration. However, how its activity is regulated still remains to be addressed. Here, we identified a Rab5 inhibitor, a long non-coding RNA, namely HITT (HIF-1α inhibitor at translation level). Our data show that HITT expression is inversely associated with advanced stages and poor prognosis of lung adenocarcinoma patients with area under receiver operating characteristics (ROC) curve (AUC) 0.6473. Further study reveals that both endogenous and exogenous HITT inhibits single-cell migration by repressing ß1 integrin endocytosis in lung adenocarcinoma. Mechanistically, HITT is physically associated with Rab5 at switch I via 1248-1347 nt and suppresses ß1 integrin endocytosis and subsequent cancer metastasis by interfering with guanine nucleotide exchange factors (GEFs) for Rab5 binding. Collectively, these findings suggest that HITT directly participates in the regulation of Rab5 activity, leading to a decreased integrin internalization and cancer metastasis, which provides important insights into a mechanistic understanding of endocytosis and cancer metastasis.

Reconfigurable Compute-In-Memory on Field-Programmable Ferroelectric Diodes.

The deluge of sensors and data generating devices has driven a paradigm shift in modern computing from arithmetic-logic centric to data-centric processing. Data-centric processing require innovations at the device level to enable novel compute-in-memory (CIM) operations. A key challenge in the construction of CIM architectures is the conflicting trade-off between the performance and their flexibility for various essential data operations. Here, we present a transistor-free CIM architecture that permits storage, search, and neural network operations on sub-50 nm thick Aluminum Scandium Nitride ferroelectric diodes (FeDs). Our circuit designs and devices can be directly integrated on top of Silicon microprocessors in a scalable process. By leveraging the field-programmability, nonvolatility, and nonlinearity of FeDs, search operations are demonstrated with a cell footprint <0.12 µm2 when projected onto 45 nm node technology. We further demonstrate neural network operations with 4-bit operation using FeDs. Our results highlight FeDs as candidates for efficient and multifunctional CIM platforms.

Exploiting the Iron Difluoride Electrochemistry by Constructing Hierarchical Electron Pathways and Cathode Electrolyte Interface.

Conversion-type cathodes such as metal fluorides, especially FeF2 and FeF3 , are potential candidates to replace intercalation cathodes for the next generation of lithium ion batteries. However, the application of iron fluorides is impeded by their poor electronic conductivity, iron/fluorine dissolution, and unstable cathode electrolyte interfaces (CEIs). A facile route to fabricate a mechanical strong electrode with hierarchical electron pathways for FeF2 nanoparticles is reported here. The FeF2 /Li cell demonstrates remarkable cycle performances with a capacity of 300 mAh g-1 after a record long 4500 cycles at 1C. Meanwhile, a record stable high area capacity of over 6 mAh cm-2 is achieved. Furthermore, ultra-high rate capabilities at 20C and 6C for electrodes with low and high mass loading, respectively, are attained. Advanced electron microscopy reveals the formation of stable CEIs. The results demonstrate that the construction of viable electronic connections and favorable CEIs are the key to boost the electrochemical performances of FeF2 cathode.

RNA interference-mediated repression of SmCPS (copalyldiphosphate synthase) expression in hairy roots of Salvia miltiorrhiza causes a decrease of tanshinones and sheds light on the functional role of SmCPS.

Tanshinones are a group of bioactive abietane-type norditerpenoid quinone compounds in Salvia miltiorrhiza. Copalyldiphosphate synthase of S. miltiorrhiza (SmCPS) is the first key enzyme in tanshinone biosynthesis from the universal diterpene precursor geranylgeranyl diphosphate. Hairy roots of S. miltiorrhiza were transformed with Agrobacterium rhizogenes carrying an RNA interference (RNAi) construct designed to silence SmCPS, and we examined the resulting SmCPS expression and tanshinone accumulation. In SmCPS­RNAi hairy roots, the transcript level of SmCPS was reduced to 26 % while the dihydrotanshinone I and cryptotanshinone levels were decreased by 53 and 38 % compared to those of the vector control hairy roots; tanshinone IIA was not detected. Therefore, the decreased expression of SmCPS caused a decrease in tanshinone levels which verifies that SmCPS is a key enzyme for tanshinone biosynthesis in S. miltiorrhiza.

Recent Development of Photochromic Polymer Systems: Mechanism, Materials, and Applications.

Photochromic polymer is defined as a series of materials based on photochromic units in polymer chains, which produces reversible color changes under irradiation with a particular wavelength. Currently, as the research progresses, it shows increasing potential applications in various fields, such as anti-counterfeiting, information storage, super-resolution imaging, and logic gates. However, there is a paucity of published reviews on the topic of photochromic polymers. Herein, this review discusses and summarizes the research progress and prospects of such materials, mainly summarizing the basic mechanisms, classification, and applications of azobenzene, spiropyran, and diarylethene photochromic polymers. Moreover, 3-dimensional (3D) printable photochromic polymers are worthy to be summarized specifically because of its innovative approach for practical application; meanwhile, the developing 3D printing technology has shown increasing potential opportunities for better applications. Finally, the current challenges and future directions of photochromic polymer materials are summarized.

Tunable afterglow for mechanical self-monitoring 3D printing structures.

Self-monitoring materials have promising applications in structural health monitoring. However, developing organic afterglow materials for self-monitoring is a highly intriguing yet challenging task. Herein, we design two organic molecules with a twisted donor-acceptor-acceptor' configuration and achieve dual-emissive afterglow with tunable lifetimes (86.1-287.7 ms) by doping into various matrices. Based on a photosensitive resin, a series of complex structures are prepared using 3D printing technology. They exhibit tunable afterglow lifetime and Young's Modulus by manipulating the photocuring time and humidity level. With sufficient photocuring or in dry conditions, a long-lived bright green afterglow without apparent deformation under external loading is realized. We demonstrate that the mechanical properties of complex 3D printing structures can be well monitored by controlling the photocuring time and humidity, and quantitively manifested by afterglow lifetimes. This work casts opportunities for constructing flexible 3D printing devices that can achieve sensing and real-time mechanical detection.

Effects of combined elicitors on tanshinone metabolic profiling and SmCPS expression in Salvia miltiorrhiza hairy root cultures.

Tanshinones are abietane-type norditerpenoid quinone natural products found in a well-known traditional Chinese medicinal herb, Salvia miltiorrhiza Bunge. The copalyl diphosphate synthase of S. miltiorrhiza (SmCPS) is the key enzyme in the first step for transformation of geranylgeranyl diphosphate (GGPP) into miltiradiene, which has recently been identified as the precursor of tanshinones. Based on previous gene-to-metabolite network, this study examined the influences of various combined elicitors on the expression of SmCPS and production of tanshinones in S. miltiorrhiza hairy root cultures. Combined elicitors were composed of three classes of elicitors, a heavy metal ion (Ag⁺), a polysaccharide (yeast extract, YE), and a plant response-signalling compound (methyl jasmonate, MJ). YE + Ag⁺, Ag⁺ + MJ, YE + MJ, and YE + Ag⁺ + MJ were the combinations we tested. The effect of elicitors on the SmCPS expression level was detected by quantitative real-time PCR (qRT-PCR), and the tanshinones accumulation responses to elicitation were analysed by Ultra Performance Liquid Chromatography (UPLC) metabolite profiling. Of these combined elicitors, the expression of SmCPS was significantly enhanced by elicitation, especially at 24 h and 36 h. Of four tanshinones detected, the contents of cryptotanshinone and dihydrotanshinone I were enhanced by treatment with YE + Ag⁺, Ag⁺ + MJ, and YE + Ag⁺ + MJ. Our results indicate that appropriate combined elicitors can enhance tanshinones production in hairy root cultures.

[Cloning and induced expression analysis of 4-hydroxy-3-methyl-but-2-enyl diphosphate reductase gene (smHDR) of Salvia miltiorrhiza].

This study reported the obtainment of the full-length cDNA of Salvia miltiorrhiza hairy roots (Abbr: SmHDR, GenBank number: JX233817), via extracting Salvia miltiorrhiza hairy roots total RNA, designing specific primers according to the transcriptome data and using the RACE strategy, and then analyzed it with bioinformatics approaches. On this basis, using the real-time PCR to detect SmHDR gene expression after Ag+ induction, and testing tanshinones contents of corresponding samples by UPLC. SmHDR has 1 647 nucleotides, and an open reading frame (ORF) encoding a protein of 463 amino acid residues. The deduced protein has isoelectric point (pI) of 5.72 and a calculated molecular weight about 51.88 kD. In the secondary structure, the percentage of alpha helix, beta turn and random coil were 35.64%, 20.30% and 44.06%, respectively. Sequence alignment and phylogenetic analysis demonstrated that SmHDR had relative close relationship to the HDR of Picrorhiza kurrooa, similar to HDR from other species of plants. Real time PCR results indicated that elicitor of Ag+ stimulated the increase of mRNA expression of SmHDR. At the same time, results of ultra performance liquid chromatography (UPLC), used to examine the accumulation of diterpenoid tanshinones in hairy roots, showed that the contents of diterpenoid tanshinones in hairy roots of Salvia miltiorrhiza were increased dramatically at 12 h after treated with Ag+, and then decreased significantly. This result showed a positive correlation between the levels of mRNA expression and tanshinones accumulation in Salvia miltiorrhiza stimulated by Ag+. The content of tanshinones was gradually raised, and it had an obvious increase at 120 h. The bioinformatics analysis and gene expression indicated that SmHDR might be involved in tanshinones biosynthesis, which laid the foundation for further study of secondary metabolic regulation mechanism of tanshinones.

Optimizing Graph Neural Network With Multiaspect Hilbert-Schmidt Independence Criterion.

The graph neural network (GNN) has demonstrated its superior power in various data mining tasks and has been widely applied in diversified fields. The core of GNN is the aggregation and combination functions, and mainstream GNN studies focus on the enhancement of these functions. However, GNNs face a common challenge, i.e., useless features contained in neighbor nodes may be integrated into the target node during the aggregation process. This leads to poor node embedding and undermines downstream tasks. To tackle this problem, this article proposes a novel GNN optimization framework GNN-MHSIC by introducing the nonparametric dependence method Hilbert-Schmidt independence criterion (HSIC) under the guidance of information bottleneck. HSIC is utilized to guide the information propagation among layers of a GNN from multiaspect views. GNN-MHSIC aims to achieve three main objectives: 1) minimizing the HSIC between the input features and the propagation layers; 2) maximizing the HSIC between the propagation layers and the ground truth; and 3) minimizing the HSIC between the propagation layers. With a multiaspect design, GNN-MHSIC can minimize the propagation of redundant information while preserving relevant information about the target node. We prove GNN-MHSIC's finite upper and lower bounds theoretically and evaluate it experimentally with four classic GNN models, including the graph convolutional network, the graph attention network (GAT), the heterogeneous GAT, and the heterogeneous graph (HG) propagation network on three widely used HGs. The results illustrate the usefulness and performance of GNN-MHSIC.

Facile fabrication of ultra-light N-doped-rGO/g-C3N4 for broadband microwave absorption.

"Thin thickness", "lightweight", "wide absorption bandwidth" and "strong absorption" are the new standards of contemporary science and technology for microwave absorption(MA) material. In this study, N-doped-rGO/g-C3N4 MA material was prepared for the first time by simple heat treatment, which the N atoms were doped into rGO and g-C3N4 was dispersed on the surface of N-doped-rGO, and its density is only 0.035 g/cm3. The impedance matching of the N-doped-rGO/g-C3N4 composite was well adjusted by decreasing the dielectric constant and attenuation constant due to the g-C3N4 semiconductor property and the graphite-like structure. Moreover, the distribution of g-C3N4 among N-doped-rGO sheets can produce more polarization effect and relaxation effect by increasing the lamellar spacing. Furthermore, the polarization loss of N-doped-rGO/g-C3N4 could be increased successfully by doping N atoms and g-C3N4. Ultimately, the MA property of N-doped-rGO/g-C3N4 composite was optimized significantly, with a loading of 5 wt%, the N-doped-rGO/g-C3N4 composite exhibited the RLmin of -49.59 dB and the effective absorption bandwidth could reach 4.56 GHz when the thickness was only 1.6 mm. The "thin thickness", "lightweight", "wide absorption bandwidth" and "strong absorption" of MA material are actually achieved by the N-doped-rGO/g-C3N4.

Emerging electro-driven technologies for phosphorus enrichment and recovery from wastewater: A review.

The recovery of phosphorus from wastewater is a critical step in addressing the scarcity of phosphorus resources. Electro-driven technologies for phosphorus enrichment have gathered significant attention due to their inherent advantages, such as mild operating conditions, absence of secondary pollution, and potential integration with other technologies. This study presents a comprehensive review of recent advancements in the field of phosphorus enrichment, with a specific focus on capacitive deionization and electrodialysis technologies. It highlights the underlying principles and effectiveness of electro-driven techniques for phosphorus enrichment while systematically comparing energy consumption, enrichment rate, and concentration factor among different technologies. Furthermore, the study provides a thorough analysis of the capacity of various technologies to selectively enrich phosphorus and proposes several methods and strategies to enhance selectivity. These insights offer valuable guidance for advancing the future development of electrochemical techniques with enhanced efficiency and effectiveness in phosphorus enrichment from wastewater.

SCUBE2 mediates bone metastasis of luminal breast cancer by modulating immune-suppressive osteoblastic niches.

Estrogen receptor (ER)-positive luminal breast cancer is a subtype with generally lower risk of metastasis to most distant organs. However, bone recurrence occurs preferentially in luminal breast cancer. The mechanisms of this subtype-specific organotropism remain elusive. Here we show that an ER-regulated secretory protein SCUBE2 contributes to bone tropism of luminal breast cancer. Single-cell RNA sequencing analysis reveals osteoblastic enrichment by SCUBE2 in early bone-metastatic niches. SCUBE2 facilitates release of tumor membrane-anchored SHH to activate Hedgehog signaling in mesenchymal stem cells, thus promoting osteoblast differentiation. Osteoblasts deposit collagens to suppress NK cells via the inhibitory LAIR1 signaling and promote tumor colonization. SCUBE2 expression and secretion are associated with osteoblast differentiation and bone metastasis in human tumors. Targeting Hedgehog signaling with Sonidegib and targeting SCUBE2 with a neutralizing antibody both effectively suppress bone metastasis in multiple metastasis models. Overall, our findings provide a mechanistic explanation for bone preference in luminal breast cancer metastasis and new approaches for metastasis treatment.

MTSS1 curtails lung adenocarcinoma immune evasion by promoting AIP4-mediated PD-L1 monoubiquitination and lysosomal degradation.

Immune checkpoint blockade (ICB) therapy targeting PD-1/PD-L1 has shown durable clinical benefits in lung cancer. However, many patients respond poorly to ICB treatment, underscoring an incomplete understanding of PD-L1 regulation and therapy resistance. Here, we find that MTSS1 is downregulated in lung adenocarcinoma, leading to PD-L1 upregulation, impairment of CD8+ lymphocyte function, and enhanced tumor progression. MTSS1 downregulation correlates with improved ICB efficacy in patients. Mechanistically, MTSS1 interacts with the E3 ligase AIP4 for PD-L1 monoubiquitination at Lysine 263, leading to PD-L1 endocytic sorting and lysosomal degradation. In addition, EGFR-KRAS signaling in lung adenocarcinoma suppresses MTSS1 and upregulates PD-L1. More importantly, combining AIP4-targeting via the clinical antidepressant drug clomipramine and ICB treatment improves therapy response and effectively suppresses the growth of ICB-resistant tumors in immunocompetent mice and humanized mice. Overall, our study discovers an MTSS1-AIP4 axis for PD-L1 monoubiquitination and reveals a potential combinatory therapy with antidepressants and ICB.

[Cloning and bioinformatics analysis of 2-c-methyl-D-erythritol 2,4-cyclodiphosphate synthase gene in Salvia miltiorrhiza].

OBJECTIVE: To clone and analysis a 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (SmMCS) full-length eDNA from Salvia miltiorrhiza hairy roots. METHOD: A full-length eDNA of SmMCS has been cloned by designing specific primers according to the transcriptome database and using the RACE strategy. ORF Finder was used to find the open reading frame of SmMCS cDNA and ClustalW has been performed to analysis the multiple amino acid sequence alignment. Phylogenetic tree has been constructed using MEGA 5. 1. Real-time quantitative PCR have been applied to detect the transcription level of SmMCS from hairy roots after elicitor Ag+ supplied. RESULT: The SmMCS cDNA sequence was obtained. The full length of SmMCS (DNA was 988 bp encoding 234 amino acids. The deduced protein had isoelectric point (pI) of 8.53 and a calculated molecular weight about 24. 6 kDa. Results of real time PCR indicated that elicitor of Ag+ stimulated the increase of mRNA expression of SmMCS in hairy roots, and were increased dramatically at 12 h. CONCLUSION: The full-length cDNA of SmMCS was cloned from S. miltiorrhiza hairy root,which can provide a gene target for further studies of tanshinones biosynthesis and terpenoid secondary metabolites.

Carbocistein improves airway remodeling in asthmatic mice.

BACKGROUND: The alleviating effects of carbocisteine (S-carboxymethylcysteine, SCMC) have been implicated in chronic obstructive pulmonary disease; however, very little is known about its mechanisms in asthma. In this study, we aimed to investigate the effects of SCMC on airway remodeling in asthmatic mice induced by ovalbumin (OVA). METHODS: The asthma mouse model was generated by OVA sensitization and stimulation and subsequently intervened by SCMC or dexamethasone. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected from each group of mice. The TGF-ß1 levels in BALF were measured by ELISA. Masson's staining was used to detect collagen fiber deposition in mouse airway tissues, while immunohistochemistry and RT-qPCR were conducted to examine the protein and mRNA expression of TGF-ß1 in mouse lung airway tissues, respectively. The correlation between TGF-ß1 mRNA expression and the area of collagen fiber deposition in airway tissues was analyzed by Pearson's correlation coefficient. RESULTS: The area of collagen fiber deposition in the airway tissues of asthmatic mice was significantly increased, while SCMC alleviated the collagen fiber deposition in the airway tissues. TGF-ß1 expression was significantly elevated in BALF and airway tissues of asthmatic mice, while SCMC inhibited TGF-ß1 expression. TGF-ß1 expression was significantly and positively correlated with collagen fiber deposition in mouse airway tissues. CONCLUSIONS: SCMC intervention improves collagen fiber deposition in airway tissues and inhibits TGF-ß1 expression in asthmatic mice.

Construction of Photoresponsive 3D Structures Based on Triphenylethylene Photochromic Building Blocks.

Photoresponsive materials have been widely used in sensing, bioimaging, molecular switches, information storage, and encryption nowadays. Although a large amount of photoresponsive materials have been reported, the construction of these smart materials into precisely prescribed complex 3D geometries is rarely studied. Here we designed a novel photoresponsive material methyl methacrylate containing triphenylethylene (TrPEF2-MA) that can be directly used for digital light processing (DLP) 3D printing. Based on TrPEF2-MA, a series of photoresponsive 3D structures with reversible color switching under ultraviolet/visible light irradiations were fabricated. These complex photoresponsive 3D structures show high resolutions (50 µm), excellent repeatability (25 cycles without fatigue), and tunable saturate color degrees. Multicomponent DLP 3D printing processes were also carried out to demonstrate their great properties in information hiding and information-carrying properties. This design strategy for constructing photoresponsive 3D structures is attractive in the area of adaptive camouflage, information hiding, information storage, and flexible electronics.

IL-20RB mediates tumoral response to osteoclastic niches and promotes bone metastasis of lung cancer.

Bone is a common site of metastasis in lung cancer, but the regulatory mechanism remains incompletely understood. Osteoclasts are known to play crucial roles in osteolytic bone metastasis by digesting bone matrix and indirectly enhancing tumor colonization. In this study, we found that IL receptor 20 subunit ß (IL-20RB) mediated a direct tumoral response to osteoclasts. Tumoral expression of IL-20RB was associated with bone metastasis of lung cancer, and functionally, IL-20RB promoted metastatic growth of lung cancer cells in bone. Mechanistically, tumor cells induced osteoclasts to secrete the IL-20RB ligand IL-19, and IL-19 stimulated IL-20RB-expressing tumor cells to activate downstream JAK1/STAT3 signaling, leading to enhanced proliferation of tumor cells in bone. Importantly, blocking IL-20RB with a neutralizing antibody significantly suppressed bone metastasis of lung cancer. Overall, our data revealed a direct protumor role of osteoclastic niche in bone metastasis and supported IL-20RB-targeting approaches for metastasis treatment.

[Research advances of diterpene synthase].

Diterpenes, an important class of natural compounds, are widely distributed in nature. As the valuable diterpenoids continue to be found, diterpene synthase in the course of diterpene synthesis get as much attention as possible. The multiformity of end-product-diterpenoids were also due to the diversity of diterpene synthase. This paper focuses on the advances in recent biosynthesis pathway of diterpene and types, cloning, catalytic mechanism, synthetic biology application.