The ligation between ERMAP, galectin-9 and dectin-2 promotes Kupffer cell phagocytosis and antitumor immunity.

Kupffer cells, the liver tissue resident macrophages, are critical in the detection and clearance of cancer cells. However, the molecular mechanisms underlying their detection and phagocytosis of cancer cells are still unclear. Using in vivo genome-wide CRISPR-Cas9 knockout screening, we found that the cell-surface transmembrane protein ERMAP expressed on various cancer cells signaled to activate phagocytosis in Kupffer cells and to control of liver metastasis. ERMAP interacted with ß-galactoside binding lectin galectin-9 expressed on the surface of Kupffer cells in a manner dependent on glycosylation. Galectin-9 formed a bridging complex with ERMAP and the transmembrane receptor dectin-2, expressed on Kupffer cells, to induce the detection and phagocytosis of cancer cells by Kupffer cells. Patients with low expression of ERMAP on tumors had more liver metastases. Thus, our study identified the ERMAP-galectin-9-dectin-2 axis as an 'eat me' signal for Kupffer cells.

Activation of polyamine catabolism promotes glutamine metabolism and creates a targetable vulnerability in lung cancer.

Polyamines are a class of small polycationic alkylamines that play essential roles in both normal and cancer cell growth. Polyamine metabolism is frequently dysregulated and considered a therapeutic target in cancer. However, targeting polyamine metabolism as monotherapy often exhibits limited efficacy, and the underlying mechanisms are incompletely understood. Here we report that activation of polyamine catabolism promotes glutamine metabolism, leading to a targetable vulnerability in lung cancer. Genetic and pharmacological activation of spermidine/spermine N1-acetyltransferase 1 (SAT1), the rate-limiting enzyme of polyamine catabolism, enhances the conversion of glutamine to glutamate and subsequent glutathione (GSH) synthesis. This metabolic rewiring ameliorates oxidative stress to support lung cancer cell proliferation and survival. Simultaneous glutamine limitation and SAT1 activation result in ROS accumulation, growth inhibition, and cell death. Importantly, pharmacological inhibition of either one of glutamine transport, glutaminase, or GSH biosynthesis in combination with activation of polyamine catabolism synergistically suppresses lung cancer cell growth and xenograft tumor formation. Together, this study unveils a previously unappreciated functional interconnection between polyamine catabolism and glutamine metabolism and establishes cotargeting strategies as potential therapeutics in lung cancer.

AAV1-hOTOF gene therapy for autosomal recessive deafness 9: a single-arm trial.

BACKGROUND: Autosomal recessive deafness 9, caused by mutations of the OTOF gene, is characterised by congenital or prelingual, severe-to-complete, bilateral hearing loss. However, no pharmacological treatment is currently available for congenital deafness. In this Article, we report the safety and efficacy of gene therapy with an adeno-associated virus (AAV) serotype 1 carrying a human OTOF transgene (AAV1-hOTOF) as a treatment for children with autosomal recessive deafness 9. METHODS: This single-arm, single-centre trial enrolled children (aged 1-18 years) with severe-to-complete hearing loss and confirmed mutations in both alleles of OTOF, and without bilateral cochlear implants. A single injection of AAV1-hOTOF was administered into the cochlea through the round window. The primary endpoint was dose-limiting toxicity at 6 weeks after injection. Auditory function and speech were assessed by appropriate auditory perception evaluation tools. All analyses were done according to the intention-to-treat principle. This trial is registered with Chinese Clinical Trial Registry, ChiCTR2200063181, and is ongoing. FINDINGS: Between Oct 19, 2022, and June 9, 2023, we screened 425 participants for eligibility and enrolled six children for AAV1-hOTOF gene therapy (one received a dose of 9 × 1011 vector genomes [vg] and five received 1·5 × 1012 vg). All participants completed follow-up visits up to week 26. No dose-limiting toxicity or serious adverse events occurred. In total, 48 adverse events were observed; 46 (96%) were grade 1-2 and two (4%) were grade 3 (decreased neutrophil count in one participant). Five children had hearing recovery, shown by a 40-57 dB reduction in the average auditory brainstem response (ABR) thresholds at 0·5-4·0 kHz. In the participant who received the 9 × 1011 vg dose, the average ABR threshold was improved from greater than 95 dB at baseline to 68 dB at 4 weeks, 53 dB at 13 weeks, and 45 dB at 26 weeks. In those who received 1·5 × 1012 AAV1-hOTOF, the average ABR thresholds changed from greater than 95 dB at baseline to 48 dB, 38 dB, 40 dB, and 55 dB in four children with hearing recovery at 26 weeks. Speech perception was improved in participants who had hearing recovery. INTERPRETATION: AAV1-hOTOF gene therapy is safe and efficacious as a novel treatment for children with autosomal recessive deafness 9. FUNDING: National Natural Science Foundation of China, National Key R&D Program of China, Science and Technology Commission of Shanghai Municipality, and Shanghai Refreshgene Therapeutics.

Transcriptome-wide subtyping of pediatric and adult T cell acute lymphoblastic leukemia in an international study of 707 cases.

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy of T cell progenitors, known to be a heterogeneous disease in pediatric and adult patients. Here we attempted to better understand the disease at the molecular level based on the transcriptomic landscape of 707 T-ALL patients (510 pediatric, 190 adult patients, and 7 with unknown age; 599 from published cohorts and 108 newly investigated). Leveraging the information of gene expression enabled us to identify 10 subtypes (G1­G10), including the previously undescribed one characterized by GATA3 mutations, with GATA3R276Q capable of affecting lymphocyte development in zebrafish. Through associating with T cell differentiation stages, we found that high expression of LYL1/LMO2/SPI1/HOXA (G1­G6) might represent the early T cell progenitor, pro/precortical/cortical stage with a relatively high age of disease onset, and lymphoblasts with TLX3/TLX1 high expression (G7­G8) could be blocked at the cortical/postcortical stage, while those with high expression of NKX2-1/TAL1/LMO1 (G9­G10) might correspond to cortical/postcortical/mature stages of T cell development. Notably, adult patients harbored more cooperative mutations among epigenetic regulators, and genes involved in JAK-STAT and RAS signaling pathways, with 44% of patients aged 40 y or above in G1 bearing DNMT3A/IDH2 mutations usually seen in acute myeloid leukemia, suggesting the nature of mixed phenotype acute leukemia.

Clinical characteristics of acute myeloid leukaemia patients with a large number of azurophilic granules: A single-centre retrospective study.

Large amounts of azurophilic granules are considered to be a morphological feature of acute promyelocytic leukaemia (APL). However, a small percentage of acute myeloid leukaemia (AML) patients also have a large number of azurophilic granules. A large cohort of 3210 AML patients in our hospital was screened to identify AML patients who had a large number of azurophilic granules. The clinical parameters of these patients were collected and compared with typical AML patients (control Group 1) and APL patients (control Group 2). The incidence of AML with a large number of azurophilic granules was 1.26%. The fibrinogen and D-dimer levels of patients in the study group were more similar to those of patients in control Group 2, as was the incidence of bleeding events. Additionally, patients in the study group had higher FLT3-ITD and NPM1 mutation rates than patients in control Group 1. Finally, patients in the study group had a higher 30-day mortality rate than those in control Group 2 (24.2% vs. 9.09%) and showed a higher 30-day mortality trend than those in control Group 1. Therefore, we should pay more attention to the prevention of coagulation dysfunction and bleeding events for these patients.

N6-Methyladenosine-Mediated Up-Regulation of FZD10 Regulates Liver Cancer Stem Cells' Properties and Lenvatinib Resistance Through WNT/ß-Catenin and Hippo Signaling Pathways.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, but there is a deficiency of early diagnosis biomarkers and therapeutic targets. Drug resistance accounts for most HCC-related deaths, yet the mechanisms underlying drug resistance remain poorly understood. METHODS: Expression of Frizzled-10 (FZD10) in liver cancer stem cells (CSCs) was identified by means of RNA sequencing and validated by means of real-time polymerase chain reaction and immunohistochemistry. In vitro and in vivo experiments were used to assess the effect of FZD10 on liver CSC expansion and lenvatinib resistance. RNA sequencing, RNA binding protein immunoprecipitation, and luciferase report assays were applied to explore the mechanism underlying FZD10-mediated liver CSCs expansion and lenvatinib resistance. RESULTS: Activation of FZD10 in liver CSCs was mediated by METTL3-dependent N6-methyladenosine methylation of FZD10 messenger RNA. Functional studies revealed that FZD10 promotes self-renewal, tumorigenicity, and metastasis of liver CSCs via activating ß-catenin and YAP1. The FZD10-ß-catenin/YAP1 axis is activated in liver CSCs and predicts poor prognosis. Moreover, FZD10-ß-catenin/c-Jun axis transcriptionally activates METTL3 expression, forming a positive feedback loop. Importantly, the FZD10/ß-catenin/c-Jun/MEK/ERK axis determines the responses of hepatoma cells to lenvatinib treatment. Analysis of patient cohort, patient-derived tumor organoids, and patient-derived xenografts further suggest that FZD10 might predict lenvatinib clinical benefit in patients with HCC. Furthermore, treatment of lenvatinib-resistant HCC with adeno-associated virus targeting FZD10 or a ß-catenin inhibitor restored lenvatinib response. CONCLUSIONS: Elevated FZD10 expression promotes expansion of liver CSCs and lenvatinib resistance, indicating that FZD10 expression is a novel prognostic biomarker and therapeutic target for human HCC.

Characterizing complete mitochondrial genome of Aquilegia amurensis and its evolutionary implications.

BACKGROUND: Aquilegia is a model system for studying the evolution of adaptive radiation. However, very few studies have been conducted on the Aquilegia mitochondrial genome. Since mitochondria play a key role in plant adaptation to abiotic stress, analyzing the mitochondrial genome may provide a new perspective for understanding adaptive evolution. RESULTS: The Aquilegia amurensis mitochondrial genome was characterized by a circular chromosome and two linear chromosomes, with a total length of 538,736 bp; the genes included 33 protein-coding genes, 24 transfer RNA (tRNA) genes and 3 ribosomal RNA (rRNA) genes. We subsequently conducted a phylogenetic analysis based on single nucleotide polymorphisms (SNPs) in the mitochondrial genomes of 18 Aquilegia species, which were roughly divided into two clades: the European-Asian clade and the North American clade. Moreover, the genes mttB and rpl5 were shown to be positively selected in European-Asian species, and they may help European and Asian species adapt to environmental changes. CONCLUSIONS: In this study, we assembled and annotated the first mitochondrial genome of the adaptive evolution model plant Aquilegia. The subsequent analysis provided us with a basis for further molecular studies on Aquilegia mitochondrial genomes and valuable information on adaptive evolution in Aquilegia.

Effects of staged multiple phytohormones application on capillary-driven attached Chlorella sp. biofilm.

Comparing with single phytohormone application, applying multiple phytohormones to microalgae-based wastewater treatment systems can offer more extensive growth-promoting and stress-protecting effects for microalgae, yet the advantage of stress-relieving salicylic acid (SA) under combined phytohormones application scenario has not been exploited. Employing the improved capillary-driven attached microalgae culturing device (CD-PBR) previously used for single phytohormone application, this study compared the effects of mixed and single phytohormone(s) addition under as low as 10-7 M dosage. In order to make the best of SA for its stress-relieving property, postponed SA addition combined with applying other phytohormone(s) at the beginning of microalgae cultivation was also investigated. Combination of 10-6 M 6-benzylaminopurine (6-BA) with 10-7 M SA was sufficient for enhancing growth-promoting effects and anti-oxidative responses for attached Chlorella sp., while indole-3-acetic acid (IAA) addition was unnecessary. Combination of 6-BA addition at the beginning while postponed SA addition on Day 4 could further sustain such beneficial effects, while removing up to 99.7% total nitrogen (TN) and 97.9% total phosphorus (TP) from the bulk liquid. These results provided innovative strategies on mixed phytohormones addition for microalgae.

Insights into aggregation dynamics of NACore peptides from coarse-grained simulations.

Alpha(α)-synuclein is closely related to the pathogenesis of Parkinson's disease (PD). The NACore, a fragment of α-synuclein, is considered to be the key region of α-synuclein that causes PD. The aggregation dynamics of NACores are studied via coarse-grained molecular dynamics simulations. We find that NACores can self-assemble into a large cluster at high concentrations. The aggregation dynamics can be divided into three stages. The growth kinetics for the first and second stages follows the power law, Smax ~ tγ , with the second stage faster than the first one. The characteristic lifetime for the high concentration is 40 times larger than that for the low concentration, implying the low fluidity. Understanding the aggregation dynamics of NACores is helpful to develop drugs for therapeutic prevention and intervention.

Glutamate dehydrogenase 1: A novel metabolic target in inhibiting acute myeloid leukaemia progression.

Glutamine metabolic reprogramming in acute myeloid leukaemia (AML) cells contributes to the decreased sensitivity to antileukemic drugs. Leukaemic cells, but not their myeloid counterparts, largely depend on glutamine. Glutamate dehydrogenase 1 (GDH1) is a regulation enzyme in glutaminolysis. However, its role in AML remains unknown. Here, we reported that GDH1 was highly expressed in AML: high GDH1 was one of the independent negative prognostic factors in AML cohort. The dependence of leukaemic cells on GDH1 was proved both in vitro and in vivo. High GDH1 promoted cell proliferation and reduced survival time of leukaemic mice. Targeting GDH1 eliminated the blast cells and delayed AML progression. Mechanistically, GDH1 knockdown inhibited glutamine uptake by downregulating SLC1A5. Moreover, GDH1 invalidation also inhibited SLC3A2 and abrogated the cystine-glutamate antiporter system Xc- . The reduced cystine and glutamine disrupted the synthesis of glutathione (GSH) and led to the dysfunction of glutathione peroxidase-4 (GPX4), which maintains the lipid peroxidation homeostasis by using GSH as a co-factor. Collectively, triggering ferroptosis in AML cells in a GSH depletion manner, GDH1 inhibition was synthetically lethal with the chemotherapy drug cytarabine. Ferroptosis induced by inhibiting GDH1 provides an actionable therapeutic opportunity and a unique target for synthetic lethality to facilitate the elimination of malignant AML cells.

circSLC25A13 acts as a ceRNA to regulate AML progression via miR-616-3p/ADCY2 axis.

Circular RNAs (circRNAs), a type of endogenous noncoding RNA (ncRNA), exert vital roles in leukemia progression and are promising prognostic factors. Here, we report a novel circRNA, circSLC25A13 (hsa_circ_0081188), which was increased in acute myeloid leukemia (AML) patients with poor overall survival (OS) comparing to patients with good prognosis. Knockdown of circSLC25A13 in AML cells inhibited proliferation and increased cell apoptosis in vitro and in vivo. Enhanced circSLC25A13 expression promoted the survival of AML cells. Mechanistically, circSLC25A13 played as a microRNA sponge of miR-616-3p, which inhibited the expression of adenylate cyclase 2 (ADCY2). Downregulation of miR-616-3p and overexpression of ADCY2 partially rescued circSLC25A13 deficient induced cell growth arrest. In summary, through competitive absorption of miR-616-3p and thereby upregulating ADCY2 expression, circSLC25A13 promoted AML progression. Moreover, circSLC25A13 may represent a potential novel biomarker for the prognosis of AML and offer a potential therapeutic target for AML treatment.

Kikuchi disease with an exuberant proliferation of large T-cells: a study of 25 cases that can mimic T-Cell lymphoma.

Exuberant large T-cell proliferations in Kikuchi disease can potentially be misdiagnosed as lymphoma. In this study, we explore their clinicopathological features and summarize key points that can be used to distinguish them from T-cell lymphoma. The cohort consisted of 25 cases of Kikuchi disease with an exuberant large T-cell proliferation, which, in part, mimicked lymphoma. The median age was 25 years with a female:male ratio of 4:1. By B-scan ultrasonography, patients presented with either isolated lymphadenopathy (68%) involving the cervical and axillary regions or generalized lymphadenopathy (32%). Histologically, lymph nodes showed paracortical and interfollicular expansion by sheets of large cells associated with karyorrhectic debris. Histiocytes and plasmacytoid dendritic cells were present in the background. No case showed complete effacement of lymph node architecture. The large cells were CD8-positive cytotoxic T-cells with a high proliferation rate. These T-cells showed decreased BCL-2 in 17 (68%) cases. CD5 expression was decreased in 10 (40%) cases. Histiocytes in the background were positive for myeloperoxidase. Clonal TRG and/or TRB rearrangements were detected in 2 of 10 (20%) cases. In conclusion, large T-cell proliferations in Kikuchi disease can be alarming at the morphologic and immunophenotypic levels and need to be distinguished from T-cell lymphoma. Clinical features helpful in the differential diagnosis include young patients and lymphadenopathy involving the cervical and axillary regions. Major pathologic features helpful in this differential diagnosis include partial involvement of the lymph node and the presence of karyorrhectic debris, crescent-shaped histiocytes, and/or loose aggregates of plasmacytoid dendritic cells.

Inhibition of USP7 upregulates USP22 and activates its downstream cancer-related signaling pathways in human cancer cells.

Deubiquitinases (DUBs) play important roles in various human cancers and targeting DUBs is considered as a novel anticancer therapeutic strategy. Overexpression of ubiquitin specific protease 7 and 22 (USP7 and USP22) are associated with malignancy, therapy resistance, and poor prognosis in many cancers. Although both DUBs are involved in the regulation of similar genes and signaling pathways, such as histone H2B monoubiquitination (H2Bub1), c-Myc, FOXP3, and p53, the interdependence of USP22 and USP7 expression has never been described. In the study, we found that targeting USP7 via either siRNA-mediated knockdown or pharmaceutical inhibitors dramatically upregulates USP22 in cancer cells. Mechanistically, the elevated USP22 occurs through a transcriptional pathway, possibly due to desuppression of the transcriptional activity of SP1 via promoting its degradation upon USP7 inhibition. Importantly, increased USP22 expression leads to significant activation of downstream signal pathways including H2Bub1 and c-Myc, which may potentially enhance cancer malignancy and counteract the anticancer efficacy of USP7 inhibition. Importantly, targeting USP7 further suppresses the in vitro proliferation of USP22-knockout (USP22-Ko) A549 and H1299 lung cancer cells and induces a stronger activation of p53 tumor suppressor signaling pathway. In addition, USP22-Ko cancer cells are more sensitive to a combination of cisplatin and USP7 inhibitor. USP7 inhibitor treatment further suppresses in vivo angiogenesis and tumor growth and induced more apoptosis in USP22-Ko cancer xenografts. Taken together, our findings demonstrate that USP7 inhibition can dramatically upregulate USP22 in cancer cells; and targeting USP7 and USP22 may represent a more effective approach for targeted cancer therapy, which warrants further study. Video Abstract.

Gold Nanoparticles Synthesized Using Various Reducing Agents and the Effect of Aging for DNA Sensing.

Gold nanoparticles (AuNPs) are one of the most commonly used reagents in colloidal science and biosensor technology. In this work, we first compared AuNPs prepared using four different reducing agents including citrate, glucose, ascorbate, and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES). At the same absorbance at the surface plasmon peak of 520-530 nm, citrate-AuNPs and glucose-AuNPs adsorbed more DNA and achieved higher affinity to the adsorbed DNA. In addition, citrate-AuNPs had better sensitivity than glucose-AuNPs for label-free DNA detection. Then, using citrate-AuNPs, the effect of aging was studied by incubation of the AuNPs at 22 °C (room temperature) and at 4 °C for up to 6 months. During aging, the colloidal stability and DNA adsorption efficiency gradually decreased. In addition, the DNA sensing sensitivity using a label-free method also dropped around 4-fold after 6 months. Heating at boiling temperature of the aged citrate-AuNPs could not rejuvenate the sensing performance. This study shows that while citrate-AuNPs are initially better than the other three AuNPs in their colloid properties and sensing properties, this edge in performance might gradually decrease due to constantly changing surface properties caused from the aging effect.

Gene editing in a Myo6 semi-dominant mouse model rescues auditory function.

Myosin VI（MYO6） is an unconventional myosin that is vital for auditory and vestibular function. Pathogenic variants in the human MYO6 gene cause autosomal-dominant or -recessive forms of hearing loss. Effective treatments for Myo6 mutation causing hearing loss are limited. We studied whether adeno-associated virus (AAV)-PHP.eB vector-mediated in vivo delivery of Staphylococcus aureus Cas9 (SaCas9-KKH)-single-guide RNA (sgRNA) complexes could ameliorate hearing loss in a Myo6WT/C442Y mouse model that recapitulated the phenotypes of human patients. The in vivo editing efficiency of the AAV-SaCas9-KKH-Myo6-g2 system on Myo6C442Y is 4.05% on average in Myo6WT/C442Y mice, which was ∼17-fold greater than editing efficiency of Myo6WT alleles. Rescue of auditory function was observed up to 5 months post AAV-SaCas9-KKH-Myo6-g2 injection in Myo6WT/C442Y mice. Meanwhile, shorter latencies of auditory brainstem response (ABR) wave I, lower distortion product otoacoustic emission (DPOAE) thresholds, increased cell survival rates, more regular hair bundle morphology, and recovery of inward calcium levels were also observed in the AAV-SaCas9-KKH-Myo6-g2-treated ears compared to untreated ears. These findings provide further reference for in vivo genome editing as a therapeutic treatment for various semi-dominant forms of hearing loss and other semi-dominant diseases.

Construction of Biocatalysts Using the P450 Scaffold for the Synthesis of Indigo from Indole.

With the increasing demand for blue dyes, it is of vital importance to develop a green and efficient biocatalyst to produce indigo. This study constructed a hydrogen peroxide-dependent catalytic system for the direct conversion of indole to indigo using P450BM3 with the assistance of dual-functional small molecules (DFSM). The arrangements of amino acids at 78, 87, and 268 positions influenced the catalytic activity. F87G/T268V mutant gave the highest catalytic activity with kcat of 1402 min-1 and with a yield of 73%. F87A/T268V mutant was found to produce the indigo product with chemoselectivity as high as 80%. Moreover, F87G/T268A mutant was found to efficiently catalyze indole oxidation with higher activity (kcat/Km = 1388 mM-1 min-1) than other enzymes, such as the NADPH-dependent P450BM3 (2.4-fold), the Ngb (32-fold) and the Mb (117-fold). Computer simulation results indicate that the arrangements of amino acid residues in the active site can significantly affect the catalytic activity of the protein. The DFSM-facilitated P450BM3 peroxygenase system provides an alternative, simple approach for a key step in the bioproduction of indigo.

Reference Genes Screening and Gene Expression Patterns Analysis Involved in Gelsenicine Biosynthesis under Different Hormone Treatments in Gelsemium elegans.

Reverse transcription quantitative polymerase chain reaction (RT-qPCR) is an accurate method for quantifying gene expression levels. Choosing appropriate reference genes to normalize the data is essential for reducing errors. Gelsemium elegans is a highly poisonous but important medicinal plant used for analgesic and anti-swelling purposes. Gelsenicine is one of the vital active ingredients, and its biosynthesis pathway remains to be determined. In this study, G. elegans leaf tissue with and without the application of one of four hormones (SA, MeJA, ETH, and ABA) known to affect gelsenicine synthesis, was analyzed using ten candidate reference genes. The gene stability was evaluated using GeNorm, NormFinder, BestKeeper, ∆CT, and RefFinder. The results showed that the optimal stable reference genes varied among the different treatments and that at least two reference genes were required for accurate quantification. The expression patterns of 15 genes related to the gelsenicine upstream biosynthesis pathway was determined by RT-qPCR using the relevant reference genes identified. Three genes 8-HGO, LAMT, and STR, were found to have a strong correlation with the amount of gelsenicine measured in the different samples. This research is the first study to examine the reference genes of G. elegans under different hormone treatments and will be useful for future molecular analyses of this medically important plant species.

HOXA10 promote pancreatic cancer progression via directly activating canonical NF-κB signaling pathway.

BACKGROUND: Although transcription factor homeobox A10 (HOXA10) plays an important role in regulating the development of the pancreas, a pathway of HOXA10 participates in pancreatic ductal adenocarcinoma (PDAC) progression has not been revealed. METHODS: Immunohistochemistry assays were applied to demonstrate the relationship between HOXA10 expression and PDAC progression. Functional assays were used to illustrate the oncogenic role of HOXA10 in PDAC progression. Regulatory mechanisms of HOXA10 induced IKKß gene transcription and the nuclear transcription factor kappa B (NF-κB) signal pathways activation were also investigated in PDAC cells. RESULTS: In the current study, we show that HOXA10 expression increased in PDAC with higher tumor stage and poor patient survival in public RNA-seq data suggesting HOXA10 is associated with PDAC progression. HOXA10 promotes PDAC cell proliferation, anchorage colony formation, and xenograft growth by activating canonical NF-κB signaling both in vitro and in vivo. Mechanically, HOXA10 up-regulates IKKß gene transcription directly and subsequently sustain the activation of NF-κB independent of tumor necrosis factor-alpha in PDAC cells. CONCLUSION: Collectively, up-regulation of HOXA10 gene expression promote cell growth and tumor progression through directly activating canonical NF-κB signaling in PDAC.

Emerging Two-Dimensional-Based Nanostructured Catalysts: Applications in Sustainable Organic Transformations.

The extension of green and sustainable materials in the preparation of heterogeneous catalysts for organic transformations has increased over the past few decades. Because of their unique and intriguing physical and chemical properties, two-dimensional (2D) nanostructured materials have attracted widespread attention and have been used in a variety of applications, such as catalysis, electronics, and energy storage. A promising pathway to enhance the performance of 2D nanomaterials is their coupling with other functional materials to form heterogeneous or hybrid structures. Herein, we discuss the use of 2D-based nanostructured catalysts for enhancing organic transformations and highlight selected examples to demonstrate the synthesis, advantages, challenges, efficiency, and reusability of the introduced heterogeneous catalysts for cross-coupling and reduction reactions.

Adsorption of DNA Oligonucleotides by Self-Assembled Metalloporphyrin Nanomaterials.

Porphyrin assemblies have controllable morphology, high biocompatibility, and good optical properties and were widely used in biomedical diagnosis and treatment. With the development of DNA biotechnology, combining DNA with porphyrin assemblies can broaden the biological applications of porphyrins. Porphyrin assemblies can serve as nanocarriers for DNA, although the fundamental interactions between them are not well understood. In this work, zinc meso-tetra(4-pyridyl)porphyrin (ZnTPyP) assemblies were prepared in the presence of various surfactants and at different pH values, yielding a variety of aggregation forms. Among them, the hexagonal stacking form exposes more pyridine substituents, and the hydrogen bonding force between the substituents and the DNA bases allows the DNA to be quickly adsorbed on the surface of the assemblies. The effects of DNA sequence and length were systematically tested. In particular, the adsorption of duplex DNA was less efficient compared to the adsorption of single-stranded DNA. This fundamental study is useful for the further combination of DNA and porphyrin assemblies to prepare new functional hybrid nanomaterials.