Accelerating bioactive peptide discovery via mutual information-based meta-learning.

Recently, machine learning methods have been developed to identify various peptide bio-activities. However, due to the lack of experimentally validated peptides, machine learning methods cannot provide a sufficiently trained model, easily resulting in poor generalizability. Furthermore, there is no generic computational framework to predict the bioactivities of different peptides. Thus, a natural question is whether we can use limited samples to build an effective predictive model for different kinds of peptides. To address this question, we propose Mutual Information Maximization Meta-Learning (MIMML), a novel meta-learning-based predictive model for bioactive peptide discovery. Using few samples from various functional peptides, MIMML can sufficiently learn the discriminative information amongst various functions and characterize functional differences. Experimental results show excellent performance of MIMML though using far fewer training samples as compared to the state-of-the-art methods. We also decipher the latent relationships among different kinds of functions to understand what meta-model learned to improve a specific task. In summary, this study is a pioneering work in the field of functional peptide mining and provides the first-of-its-kind solution for few-sample learning problems in biological sequence analysis, accelerating the new functional peptide discovery. The source codes and datasets are available on https://github.com/TearsWaiting/MIMML.

Giant Correlated Gap and Possible Room-Temperature Correlated States in Twisted Bilayer MoS_{2}.

Moiré superlattices have emerged as an exciting condensed-matter quantum simulator for exploring the exotic physics of strong electronic correlations. Notable progress has been witnessed, but such correlated states are achievable usually at low temperatures. Here, we report evidence of possible room-temperature correlated electronic states and layer-hybridized SU(4) model simulator in AB-stacked MoS_{2} homobilayer moiré superlattices. Correlated insulating states at moiré band filling factors v=1, 2, 3 are unambiguously established in twisted bilayer MoS_{2}. Remarkably, the correlated electronic state at v=1 shows a giant correlated gap of ∼126 meV and may persist up to a record-high critical temperature over 285 K. The realization of a possible room-temperature correlated state with a large correlated gap in twisted bilayer MoS_{2} can be understood as the cooperation effects of the stacking-specific atomic reconstruction and the resonantly enhanced interlayer hybridization, which largely amplify the moiré superlattice effects on electronic correlations. Furthermore, extreme large nonlinear Hall responses up to room temperature are uncovered near correlated electronic states, demonstrating the quantum geometry of moiré flat conduction band.

The combinational nano-immunotherapy of ferumoxytol and poly(I:C) inhibits melanoma via boosting anti-angiogenic immunity.

Angiogenesis plays a key role in the progression and metastasis of melanoma, and the pro-angiogenic effect of macrophages is one major reason for the failure of current anti-angiogenic therapies. Here, a nano-immunotherapy combining ferumoxytol and poly(I:C) (ferumoxytol/poly(I:C)) has been developed to boost the anti-angiogenic activities of macrophages to inhibit melanoma. Our findings demonstrated that ferumoxytol/poly(I:C) was a highly efficacious anti-tumor therapy with limited toxicity. Both in vivo and in vitro experiments indicated that this combination was successful in impeding angiogenesis. Ferumoxytol/poly(I:C) was demonstrated to reduce the viability of endothelial cells, thus hindering tube formation. Particularly, ferumoxytol/poly(I:C) was able to polarize macrophages to the M1 phenotype and decrease the expression of vascular endothelial growth factor, which in turn amplified the anti-angiogenic properties of ferumoxytol/poly(I:C). This combination of ferumoxytol/poly(I:C) nano-immunotherapy enriches the anti-angiogenic therapeutic nature of ferumoxytol and will shed new light on the treatment of melanoma.

Development of an experiment-split method for benchmarking the generalization of a PTM site predictor: Lysine methylome as an example.

Many computational classifiers have been developed to predict different types of post-translational modification sites. Their performances are measured using cross-validation or independent test, in which experimental data from different sources are mixed and randomly split into training and test sets. However, the self-reported performances of most classifiers based on this measure are generally higher than their performances in the application of new experimental data. It suggests that the cross-validation method overestimates the generalization ability of a classifier. Here, we proposed a generalization estimate method, dubbed experiment-split test, where the experimental sources for the training set are different from those for the test set that simulate the data derived from a new experiment. We took the prediction of lysine methylome (Kme) as an example and developed a deep learning-based Kme site predictor (called DeepKme) with outstanding performance. We assessed the experiment-split test by comparing it with the cross-validation method. We found that the performance measured using the experiment-split test is lower than that measured in terms of cross-validation. As the test data of the experiment-split method were derived from an independent experimental source, this method could reflect the generalization of the predictor. Therefore, we believe that the experiment-split method can be applied to benchmark the practical performance of a given PTM model. DeepKme is free accessible via https://github.com/guoyangzou/DeepKme.

Identification and function analysis of an immune deficiency homolog in swimming crab, Portunus trituberculatus.

The immune deficiency (IMD) pathway is involved in both antiviral and antibacterial immune responses in Drosophila. IMD protein is the key adaptor to link the extracellular signal and the intracellular reaction to initiate the signal transduction in IMD pathway. In present study, the cDNA of the IMD (Pt-IMD) was identified from a marine crab, Portunus trituberculatus. The Pt-IMD is predicted to encode 170 amino acids with a death domain. Real-Time quantitative PCR analysis showed that Pt-IMD was constitutively expressed in hemocytes, intestine, gill, heart, muscle and hepatopancreas in normal crab. Moreover, the transcript of Pt-IMD in large-granule hemocytes is approximately 6-fold higher than semi-granular cells and agranular cells. Intracellular localization showed Pt-IMD was distributed mainly in the cytoplasm when it was over-expressed in Drosophila Schneider 2 (S2) cell. Functionally, over-expression of Pt-IMD could activate the promoters of Drosophila antimicrobial peptide genes (AMPs) in S2 cell. Furthermore, Pt-IMD expression was also knock-down by RNAi to determine the function of Pt-IMD on regulation of the expression of different antimicrobial peptides (AMPs) in crab. In the primary cultured hemocytes challenged with or without Vibrio alginolyticus, after Pt-IMD was knocked-down by specific long double strand RNA, the expression of anti-lipopolysaccharide factor1 (ALF1), ALF3, crustin1, crustin3, arasin2, hyastatin1and hyastatin3 have been significantly inhibited in normal cell or bacterial infected cell, while the expression of lysozyme was normal in non-infected cells and was significantly induced in bacterial infected cells, which compared to the non-specific dsRNA treated cells.

Enhanced thermal properties for nanoencapsulated phase change materials with functionalized graphene oxide (FGO) modified PMMA.

A novel kind of nanoencapsulated phase change materials containing n-octadecane and n-butyl stearate as binary cores and functionalized graphene oxide modified poly(methyl methacrylate) as hybrid shells (FGO/PMMA-NanoPCMs) with superior thermal storage capability was successfully prepared by surfactant-free emulsion polymerization with reactive emulsifiers. The morphology, structure and thermal stability of graphene oxide (GO) and functionalized graphene oxide (FGO) were characterized by SEM, FT-IR, XRD and TGA. The results showed that GO was successfully modified by methacryloxy trimethoxyl silane (KH-570) into the reduced hydrophilic FGO. Furthermore, the morphology, particle size, chemical structure and thermal properties of PMMA-NanoPCMs and FGO/PMMA-NanoPCMs were also measured by TEM, FT-IR, XRD, DSC and TGA. The results indicated that FGO/PMMA-NanoPCMs exhibited a regular spherical profile with diameter around 100 nm and a well-defined core-shell structure. Moreover, the loading of FGO on PMMA-NanoPCMs effectively improved the thermal conductivity, latent enthalpy and thermal stability of nanocapsules. More importantly, in comparison with PMMA-NanoPCMs, FGO/PMMA-NanoPCMs had more significant thermal storage and temperature regulation performance when applied to cotton fabrics. It can be considered that the resultant FGO/PMMA-NanoPCMs will have a high feasibility and a great promise in the application of intelligent thermoregulation fabric.

Toll-like receptor 3 agonist poly I:C reinforces the potency of cytotoxic chemotherapy via the TLR3-UNC93B1-IFN-ß signaling axis in paclitaxel-resistant colon cancer.

Type I interferon (IFN) signaling in neoplastic cells has a chemo-sensitizing effect in cancer therapy. Toll-like receptor 3 (TLR3) activation promotes IFN-ß production, which induces apoptosis and impairs proliferation in some cancer cells. Herein, we tested whether the TLR3 agonist polyinosinic: polycytidylic acid (poly I:C) can improve chemotherapeutic efficacy in paclitaxel (PTX) resistant cell lines. Human colon cancer cell lines HCT116, SW620, HCT-8 (sensitive to PTX), and HCT-8/PTX (resistant to PTX) were treated with poly I:C and the cell viability was measured. Results showed that poly I:C specifically impaired the cell viability of HCT-8/PTX by simultaneously promoting cell apoptosis and inhibiting cell proliferation. In addition, when TLR3 was overexpressed in HCT-8/PTX cells, we found that TLR3 contributed to the production of IFN-ß that reduced cell viability, and poly I:C preferentially activated the TLR3-UNC93B1 signaling pathway to mediate this effect. Moreover, cotreatment of poly I:C and PTX acted synergistically to induce cell apoptosis of HCT-8/PTX via upregulating the expression of TLR3 and its molecular chaperone UNC93B1, assisting in the secretion of IFN-ß. Notably, a combination of poly I:C and PTX synergistically inhibited the PTX-resistant tumor growth in vivo without side effects. In conclusion, our studies demonstrate that poly I:C reinforces the potency of cytotoxic chemotherapeutics in PTX-resistant cell line through the TLR3-UNC93B1-IFN-ß signaling pathway, which supplies a novel mechanism of poly I:C for the chemotherapy sensitizing effect in a PTX-resistant tumor.

Characterization, subcellular localization and function analysis of myeloid differentiation factor 88 (Pt-MyD88) in swimming crab, Portunus trituberculatus.

Myeloid differentiation factor 88 (MyD88) is a universal and essential adaptor protein required for the Toll-like receptors (TLRs) pathway activation in invertebrates as well as in vertebrates. Herein, we characterized a MyD88 (Pt-MyD88) cDNA sequence in the swimming crab (Portunus trituberculatus). The Pt-MyD88 ORF is predicted to encode 469 peptides with an N-terminal death domain and a typical C-terminal TIR domain. Real-Time quantitative PCR analysis showed that the Pt-MyD88 transcriptions were constitutively expressed in hemocytes, gill, intestine, heart and muscle in normal crab. The expressions of Pt-MyD88 would be down-regulated by V. alginolyticus or LPS challenge, and be up-regulated by WSSV infection in hemocytes. Intracellular localization showed Pt-MyD88 was distributed mainly in the cytoplasm when it was over-expressed in human cell HEK293T or in Drosophila Schneider 2 (S2). Functionally, over-expression of Pt-MyD88 could either activate the NF-κB in HEK293T cells or activate the promoters of Drosophila antimicrobial peptide genes (AMPs) in S2 cell. In primary cultured hemocytes of swimming crab, after Pt-MyD88 was knocked-down by specific long double strand RNA, the expression of anti-lipopolysaccharide factor1 (ALF1), hyastatin3, crustin1 and crustin3 have been significantly inhibited, while the expression of other AMPs is normal compared to non-specific dsRNA treated cells.

The First Result of Relative Positioning and Velocity Estimation Based on CAPS.

The Chinese Area Positioning System (CAPS) is a new positioning system developed by the Chinese Academy of Sciences based on the communication satellites in geosynchronous orbit. The CAPS has been regarded as a pilot system to test the new technology for the design, construction and update of the BeiDou Navigation Satellite System (BDS). The system structure of CAPS, including the space, ground control station and user segments, is almost like the traditional Global Navigation Satellite Systems (GNSSs), but with the clock on the ground, the navigation signal in C waveband, and different principles of operation. The major difference is that the CAPS navigation signal is first generated at the ground control station, before being transmitted to the satellite in orbit and finally forwarded by the communication satellite transponder to the user. This design moves the clock from the satellite in orbit to the ground. The clock error can therefore be easily controlled and mitigated to improve the positioning accuracy. This paper will present the performance of CAPS-based relative positioning and velocity estimation as assessed in Beijing, China. The numerical results show that, (1) the accuracies of relative positioning, using only code measurements, are 1.25 and 1.8 m in the horizontal and vertical components, respectively; (2) meanwhile, they are about 2.83 and 3.15 cm in static mode and 6.31 and 10.78 cm in kinematic mode, respectively, when using the carrier-phase measurements with ambiguities fixed; and (3) the accuracy of the velocity estimation is about 0.04 and 0.11 m/s in static and kinematic modes, respectively. These results indicate the potential application of CAPS for high-precision positioning and velocity estimation and the availability of a new navigation mode based on communication satellites.

Dihydroartemisinin and Curcumin Synergistically Induce Apoptosis in SKOV3 Cells Via Upregulation of MiR-124 Targeting Midkine.

BACKGROUND/AIM: Women with advanced ovarian carcinoma are less likely to receive platinum-based chemotherapy and surgery due to a greater risk of cytotoxicity and poorer outcomes. We attempted to improve a promising therapy against ovarian cancer by using a combination of dihydroartemisinin (DHA) and curcumin (Cur). METHODS: Human ovarian cancer SKOV3 cells were treated with DHA, Cur alone, or a combination of both. The viability of SKOV3 cells was measured by Cell Counting Kit-8 (CCK-8) and a colony formation assay. The cell cycle and apoptosis of SKOV3 cells were monitored by flow cytometry. The mRNA and protein expression levels of target genes were respectively examined by qRT-PCR and western blot. The biological effects of miR-124 on midkine (MK) were verified by a luciferase activity analysis. RESULTS: Combined treatment of DHA and Cur synergistically decreased cell viability, arrested cell cycle, and promoted apoptosis in SKOV3 cells. Moreover, it significantly attenuated the expression of oncogene MK and synergistically upregulated the expression of miR-124. Furthermore, miR-124 was verified to bind directly to the 3'-untranslated region of MK mRNA, resulting in mRNA degradation and reduced MK protein levels. The combination of DHA with Cur significantly inhibited tumor growth in xenograft nude mice without obvious toxicity. CONCLUSION: Co-treatment with DHA and Cur exhibited a synergistic anti-tumor effect on SKOV3 cells both in vitro and in vivo.

MiR-495 Promotes Senescence of Mesenchymal Stem Cells by Targeting Bmi-1.

BACKGROUND/AIMS: Mesenchymal stem cells (MSCs) play an important role in regulating angiogenesis and immune balance. Abnormal proliferation and function of MSCs were reported at maternal fetal interface in patients with pre-eclampsia (PE). Micro-RNA-495 was known to be upregulated in the MSCs derived from patients with PE. However, it is not clear whether the up-regulated miR-495 is related to the pathogenesis of PE. METHODS: We analyzed the expression of miR-495 in MSCs and umbilical cords derived from healthy pregnancies (NC) and PE, then we upregulated or downregulated the expression of miR-495 in MSCs derived from NC and tested the proliferation, apoptosis, migration, invasion, tube formation and senescence. RESULTS: In the current study, we found that the expression of miR-495 was significantly increased in both umbilical cord tissues and MSCs in patients with severe PE. Overexpressing miR-495 arrested cell cycle in S phase and promoted cell apoptosis. The supernatants from miR-495-overexpressed-MSCs inhibited the migration of MSCs and HTR-8/SVneo, invasion of HTR-8/SVneo and tube formation of HUVEC, while si-miR-495 had the opposite effects. Furthermore, we analyzed the senescence related ß-galactosidase activity and CD146 and found that miR-495 induced the senescence of MSCs. Molecular mechanism studies confirmed that Bmi-1 mediated these effects of miR-495 on MSCs. CONCLUSION: Taken together, our data demonstrated that miR-495 induced senescence of MSCs may be involved in the pathogenesis of PE.

MiR-212-5p Suppresses the Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer by Targeting Prrx2.

BACKGROUND/AIMS: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Our study investigated the functional role of miR-212-5p in TNBC. METHODS: Realtime PCR was used to quantify miR-212-5p expression levels in 30 paired TNBC samples and adjacent normal tissues. Wound healing and Transwell assays were used to evaluate the effects of miR-212-5p expression on the invasiveness of TNBC cells. Luciferase reporter and Western blot assays were used to verify whether the mRNA encoding Prrx2 is a major target of miR-212-5p. RESULTS: MiR-212-5p was downregulated in TNBC, and its expression levels were related to tumor size, lymph node status and vascular invasion in breast cancer. We also observed that the miR-212-5p expression level was significantly correlated with a better prognosis in TNBC. Ectopic expression of miR-212-5p induced upregulation of E-cadherin expression and downregulation of vimentin expression. The expression of miR212-5p also suppressed the migration and invasion capacity of mesenchymal-like cancer cells accompanied by a morphological shift towards the epithelial phenotype. Moreover, our study observed that miR-212-5p overexpression significantly suppressed Prrx2 by targeting its 3'-untranslated region (3'-UTR) region, and Prrx2 overexpression partially abrogated miR-212-5p-mediated suppression. CONCLUSIONS: Our study demonstrated that miR-212-5p inhibits TNBC from acquiring the EMT phenotype by downregulating Prrx2, thereby inhibiting cell migration and invasion during cancer progression.

Silencing of Prrx1b suppresses cellular proliferation, migration, invasion and epithelial-mesenchymal transition in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive tumour subtype associated with poor prognosis. The mechanisms involved in TNBC progression remains largely unknown. To date, there are no effective therapeutic targets for this tumour subtype. Paired-related homeobox 1b (Prrx1b), one of major isoforms of Prrx1, has been identified as a new epithelial-mesenchymal transition (EMT) inducer. However, the function of Prrx1b in TNBC has not been elucidated. In this study, we found that Prrx1b was significantly up-regulated in TNBC and associated with tumour size and vascular invasion of breast cancer. Silencing of Prrx1b suppressed the proliferation, migration and invasion of basal-like cancer cells. Moreover, silencing of Prrx1b prevented Wnt/ß-catenin signaling pathway and induced the mesenchymal-epithelial transition (MET). Taken together, our data indicated that Prrx1b may be an important regulator of EMT in TNBC cells and a new therapeutic target for interventions against TNBC invasion and metastasis.

Genomic survey sequencing for development and validation of single-locus SSR markers in peanut (Arachis hypogaea L.).

BACKGROUND: Single-locus markers have many advantages compared with multi-locus markers in genetic and breeding studies because their alleles can be assigned to particular genomic loci in diversity analyses. However, there is little research on single-locus SSR markers in peanut. Through the de novo assembly of DNA sequencing reads of A. hypogaea, we developed single-locus SSR markers in a genomic survey for better application in genetic and breeding studies of peanut. RESULTS: In this study, DNA libraries with four different insert sizes were used for sequencing with 150 bp paired-end reads. Approximately 237 gigabases of clean data containing 1,675,631,984 reads were obtained after filtering. These reads were assembled into 2,102,446 contigs with an N50 length of 1,782 bp, and the contigs were further assembled into 1,176,527 scaffolds with an N50 of 3,920 bp. The total length of the assembled scaffold sequences was 2.0 Gbp, and 134,652 single-locus SSRs were identified from 375,180 SSRs. Among these developed single-locus SSRs, trinucleotide motifs were the most abundant, followed by tetra-, di-, mono-, penta- and hexanucleotide motifs. The most common motif repeats for the various types of single-locus SSRs have a tendency to be A/T rich. A total of 1,790 developed in silico single-locus SSR markers were chosen and used in PCR experiments to confirm amplification patterns. Of them, 1,637 markers that produced single amplicons in twelve inbred lines were considered putative single-locus markers, and 290 (17.7 %) showed polymorphisms. A further F2 population study showed that the segregation ratios of the 97 developed SSR markers, which showed polymorphisms between the parents, were consistent with the Mendelian inheritance law for single loci (1:2:1). Finally, 89 markers were assigned to an A. hypogaea linkage map. A subset of 100 single-locus SSR markers was shown to be highly stable and universal in a collection of 96 peanut accessions. A neighbor-joining tree of this natural population showed that genotypes have obviously correlation with botanical varieties. CONCLUSIONS: We have shown that the detection of single-locus SSR markers from a de novo genomic assembly of a combination of different-insert-size libraries is highly efficient. This is the first report of the development of genome-wide single-locus markers for A. hypogaea, and the markers developed in this study will be useful for gene tagging, sequence scaffold assignment, linkage map construction, diversity analysis, variety identification and association mapping in peanut.

Smart Device-Supported BDS/GNSS Real-Time Kinematic Positioning for Sub-Meter-Level Accuracy in Urban Location-Based Services.

Using mobile smart devices to provide urban location-based services (LBS) with sub-meter-level accuracy (around 0.5 m) is a major application field for future global navigation satellite system (GNSS) development. Real-time kinematic (RTK) positioning, which is a widely used GNSS-based positioning approach, can improve the accuracy from about 10-20 m (achieved by the standard positioning services) to about 3-5 cm based on the geodetic receivers. In using the smart devices to achieve positioning with sub-meter-level accuracy, a feasible solution of combining the low-cost GNSS module and the smart device is proposed in this work and a user-side GNSS RTK positioning software was developed from scratch based on the Android platform. Its real-time positioning performance was validated by BeiDou Navigation Satellite System/Global Positioning System (BDS/GPS) combined RTK positioning under the conditions of a static and kinematic (the velocity of the rover was 50-80 km/h) mode in a real urban environment with a SAMSUNG Galaxy A7 smartphone. The results show that the fixed-rates of ambiguity resolution (the proportion of epochs of ambiguities fixed) for BDS/GPS combined RTK in the static and kinematic tests were about 97% and 90%, respectively, and the average positioning accuracies (RMS) were better than 0.15 m (horizontal) and 0.25 m (vertical) for the static test, and 0.30 m (horizontal) and 0.45 m (vertical) for the kinematic test.

[Studies on chemical constituents of Isodon excisoides].

The chemical constituents of the water extraction of the aerial parts of Isodon excisoides were investigated by various chromatographic methods including D-101 macroporous adsorptive resins, silica gel, Sephadex LH-20, MCI and semi-preparative HPLC. As a result, six compounds were separated and purified.By analyses of the HR-ESI-MS, 1D and 2D NMR spectra, their structures were determined as 3-O-ß-D-allopyranosyl-1-octen-3-ol(1), blumenolA (2), lumichrome (3), loliolide(4), cirsiliol(5) and pedalitin(6). Compound 1 was a new compound, and compounds 2-4 were isolated from this plant for the first time.

Decitabine suppresses MDSC-induced immunosuppression through dual functional mechanism and inhibits melanoma metastasis.

Myeloid-derived suppressor cells (MDSCs) play a crucial role in promoting melanoma metastasis. Reprogramming MDSCs into mature M1 macrophages has emerged as a strategy to inhibit metastasis. Decitabine (Dec) is known to eradicate MDSCs and suppress tumor growth. In this study, we provide evidence that Dec not only reduces the MDSC population by inducing apoptosis, arresting cell cycle, and impairing recruitment, but also suppresses their immunosuppressive function by downregulating related genes and facilitating differentiation into M1 macrophages. Transcriptomic analysis of Dec-treated MDSCs revealed a marked downregulation of immunosuppressive genes including S100a9, S100a8, Vegf, Cxcr2, and Nos2. Meanwhile, M1 macrophage-associated genes involved in immune activation were upregulated, such as Ddx58, Isg15, Tap1, Ccl5, Cxcl9, and Cxcl10. Further bioinformatic analysis indicated that Dec promotes MDSC-to-M1 macrophage differentiation and activates innate immune pathways including NOD-like signaling to enhance anti-tumor immunity. Time-course studies implied that Dec upregulates myeloid transcription factor Irf7 to initiate MDSC differentiation and orchestrate the anti-tumor immune response. Collectively, our study unveils a novel dual-functional mechanism of Dec as both a cytotoxic agent reducing MDSCs and an inducer of their differentiation into M1 macrophages, thereby alleviating immunosuppression. This highlights Dec's potential for clinical melanoma metastasis suppression.

Enhancing anti-angiogenic immunotherapy for melanoma through injectable metal-organic framework hydrogel co-delivery of combretastatin A4 and poly(I:C).

The interplay between vascularization and macrophage-induced immune suppression plays a crucial role in melanoma treatment. In this study, we propose a novel combination approach to combat melanoma by simultaneously inhibiting tumor vascularization and enhancing macrophage-mediated anti-tumor responses. We investigate the potential of combining combretastatin A4 (CA4), a vascular-disrupting agent, with poly(I:C) (PIC), an immunostimulatory adjuvant. This combination approach effectively suppresses melanoma cell proliferation, disrupts vascularization, and promotes macrophage polarization towards the M1 phenotype for melanoma suppression. To facilitate efficient co-delivery of CA4 and PIC for enhanced anti-angiogenic immunotherapy, we develop an injectable metal-organic framework hydrogel using Zeolitic Imidazolate Framework-8 (ZIF-8) and hyaluronic acid (HA) (ZIF-8/HA). Our findings demonstrate that ZIF-8 enables efficient loading of CA4 and enhances the stability of PIC against RNAase degradation in vitro. Furthermore, the developed co-delivery hydrogel system, PIC/CA4@ZIF-8/HA, exhibits improved rheological properties, good injectability and prolonged drug retention. Importantly, in vivo experiments demonstrate that the PIC/CA4@ZIF-8/HA formulation significantly reduces the dosage and administration frequency while achieving a more pronounced therapeutic effect. It effectively inhibits melanoma growth by suppressing angiogenesis, destroying blood vessels, promoting M1 macrophage infiltration, and demonstrating excellent biocompatibility. In conclusion, our study advances anti-angiogenic immunotherapy for melanoma through the potent combination of PIC/CA4, particularly when administered using the PIC/CA4@ZIF-8/HA formulation. These findings provide a new perspective on clinical anti-angiogenic immunotherapy for melanoma, emphasizing the importance of targeting tumor vascularization and macrophage-mediated immune suppression simultaneously.

Transcriptional Regulation and Gene Mapping of Internode Elongation and Late Budding in the Chinese Cabbage Mutant lcc.

Two important traits of Chinese cabbage, internode length and budding time, destroy the maintenance of rosette leaves in the vegetative growth stage and affect flowering in the reproductive growth stage. Internodes have received much attention and research in rice due to their effect on lodging resistance, but they are rarely studied in Chinese cabbage. In Chinese cabbage, internode elongation affects not only the maintenance of rosette leaves but also bolting and yield. Budding is also an important characteristic of Chinese cabbage entering reproductive growth. Although many studies have reported on flowering and bolting, studies on bud emergence and the timing of budding are scarce. In this study, the mutant lcc induced by EMS (Ethyl Methane Sulfonate) was used to study internode elongation in the seedling stage and late budding in the budding stage. By comparing the gene expression patterns of mutant lcc and wild-type A03, 2280 differentially expressed genes were identified in the seedling stage, 714 differentially expressed genes were identified in the early budding stage, and 1052 differentially expressed genes were identified in the budding stage. Here, the transcript expression patterns of genes in the plant hormone signaling and clock rhythm pathways were investigated in relation to the regulation of internode elongation and budding in Chinese cabbage. In addition, an F2 population was constructed with the mutants lcc and R500. A high-density genetic map with 1602 marker loci was created, and QTLs for internode length and budding time were identified. Specifically, five QTLs for internode length and five QTLs for budding time were obtained. According to transcriptome data analysis, the internode length candidate gene BraA02g005840.3C (PIN8) and budding time candidate genes BraA02g003870.3C (HY5-1) and BraA02g005190.3C (CHS-1) were identified. These findings provide insight into the regulation of internode length and budding time in Chinese cabbage.

Eight In. Wafer-Scale Epitaxial Monolayer MoS2.

Large-scale, high-quality, and uniform monolayer molybdenum disulfide (MoS2) films are crucial for their applications in next-generation electronics and optoelectronics. Epitaxy is a mainstream technique for achieving high-quality MoS2 films and is demonstrated at a wafer scale up to 4-in. In this study, the epitaxial growth of 8-in. wafer-scale highly oriented monolayer MoS2 on sapphire is reported as with excellent spatial homogeneity, using a specially designed vertical chemical vapor deposition (VCVD) system. Field effect transistors (FETs) based on the as-grown 8-in. wafer-scale monolayer MoS2 film are fabricated and exhibit high performances, with an average mobility and an on/off ratio of 53.5 cm2 V-1 s-1 and 107, respectively. In addition, batch fabrication of logic devices and 11-stage ring oscillators are also demonstrated, showcasing excellent electrical functions. This work may pave the way of MoS2 in practical industry-scale applications.