Single-Cell Analyses Inform Mechanisms of Myeloid-Targeted Therapies in Colon Cancer.

Single-cell RNA sequencing (scRNA-seq) is a powerful tool for defining cellular diversity in tumors, but its application toward dissecting mechanisms underlying immune-modulating therapies is scarce. We performed scRNA-seq analyses on immune and stromal populations from colorectal cancer patients, identifying specific macrophage and conventional dendritic cell (cDC) subsets as key mediators of cellular cross-talk in the tumor microenvironment. Defining comparable myeloid populations in mouse tumors enabled characterization of their response to myeloid-targeted immunotherapy. Treatment with anti-CSF1R preferentially depleted macrophages with an inflammatory signature but spared macrophage populations that in mouse and human expresses pro-angiogenic/tumorigenic genes. Treatment with a CD40 agonist antibody preferentially activated a cDC population and increased Bhlhe40+ Th1-like cells and CD8+ memory T cells. Our comprehensive analysis of key myeloid subsets in human and mouse identifies critical cellular interactions regulating tumor immunity and defines mechanisms underlying myeloid-targeted immunotherapies currently undergoing clinical testing.

Landscape and Dynamics of Single Immune Cells in Hepatocellular Carcinoma.

The immune microenvironment of hepatocellular carcinoma (HCC) is poorly characterized. Combining two single-cell RNA sequencing technologies, we produced transcriptomes of CD45+ immune cells for HCC patients from five immune-relevant sites: tumor, adjacent liver, hepatic lymph node (LN), blood, and ascites. A cluster of LAMP3+ dendritic cells (DCs) appeared to be the mature form of conventional DCs and possessed the potential to migrate from tumors to LNs. LAMP3+ DCs also expressed diverse immune-relevant ligands and exhibited potential to regulate multiple subtypes of lymphocytes. Of the macrophages in tumors that exhibited distinct transcriptional states, tumor-associated macrophages (TAMs) were associated with poor prognosis, and we established the inflammatory role of SLC40A1 and GPNMB in these cells. Further, myeloid and lymphoid cells in ascites were predominantly linked to tumor and blood origins, respectively. The dynamic properties of diverse CD45+ cell types revealed by this study add new dimensions to the immune landscape of HCC.

Landscape of Infiltrating T Cells in Liver Cancer Revealed by Single-Cell Sequencing.

Systematic interrogation of tumor-infiltrating lymphocytes is key to the development of immunotherapies and the prediction of their clinical responses in cancers. Here, we perform deep single-cell RNA sequencing on 5,063 single T cells isolated from peripheral blood, tumor, and adjacent normal tissues from six hepatocellular carcinoma patients. The transcriptional profiles of these individual cells, coupled with assembled T cell receptor (TCR) sequences, enable us to identify 11 T cell subsets based on their molecular and functional properties and delineate their developmental trajectory. Specific subsets such as exhausted CD8+ T cells and Tregs are preferentially enriched and potentially clonally expanded in hepatocellular carcinoma (HCC), and we identified signature genes for each subset. One of the genes, layilin, is upregulated on activated CD8+ T cells and Tregs and represses the CD8+ T cell functions in vitro. This compendium of transcriptome data provides valuable insights and a rich resource for understanding the immune landscape in cancers.

Liver tumour immune microenvironment subtypes and neutrophil heterogeneity.

The heterogeneity of the tumour immune microenvironment (TIME), organized by various immune and stromal cells, is a major contributing factor of tumour metastasis, relapse and drug resistance1-3, but how different TIME subtypes are connected to the clinical relevance in liver cancer remains unclear. Here we performed single-cell RNA-sequencing (scRNA-seq) analysis of 189 samples collected from 124 patients and 8 mice with liver cancer. With more than 1 million cells analysed, we stratified patients into five TIME subtypes, including immune activation, immune suppression mediated by myeloid or stromal cells, immune exclusion and immune residence phenotypes. Different TIME subtypes were spatially organized and associated with chemokine networks and genomic features. Notably, tumour-associated neutrophil (TAN) populations enriched in the myeloid-cell-enriched subtype were associated with an unfavourable prognosis. Through in vitro induction of TANs and ex vivo analyses of patient TANs, we showed that CCL4+ TANs can recruit macrophages and that PD-L1+ TANs can suppress T cell cytotoxicity. Furthermore, scRNA-seq analysis of mouse neutrophil subsets revealed that they are largely conserved with those of humans. In vivo neutrophil depletion in mouse models attenuated tumour progression, confirming the pro-tumour phenotypes of TANs. With this detailed cellular heterogeneity landscape of liver cancer, our study illustrates diverse TIME subtypes, highlights immunosuppressive functions of TANs and sheds light on potential immunotherapies targeting TANs.

Rational design and synthesis of triazene-amonafide derivatives as novel potential antitumor agents causing oxidative damage towards DNA through intercalation mode.

In this work, we rationally designed and synthesized two novel triazene-amonafide derivatives 2-(2-(diisopropylamino)ethyl)-5-(3,3-dimethyltriaz-1-en-1-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (D-11) and 5-(3,3-diethyltriaz-1-en-1-yl)-2-(2-(diisopropylamino)ethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (D-12) as potential antitumor agents. The DNA damage induced by the intercalation mode of D-11 (D-12) towards DNA was electrochemically detected through the construction of efficient biosensors. The consecutive processes of reversible redox of naphthylimide ring and irreversible oxidation of triazene moiety were elucidated on the surface of glassy carbon electrode (GCE) by CV, SWV, and DPV methods. Electrochemical biosensors were obtained through the immobilization of ctDNA, G-quadruplexes, poly(dG), and poly(dA), respectively, on the clean surface of GCE. After the incubation of biosensors with D-11 or D-12, the peaks of dGuo and dAdo decreased prominently, and the peak of 8-oxoGua appeared at +0.50 V, suggesting that the interaction between D-11 (D-12) and DNA could result in the oxidative damage of guanine. Unexpected, the as-prepared DNA biosensor possessed satisfactory anti-interference property and good practicability in real samples. UV-vis and fluorescence spectra, and gel electrophoresis assays were employed to further confirm the intercalation mode of D-11 (D-12) towards DNA base pairs. Moreover, D-11 was proved to exhibit stronger anti-proliferation activity than mitionafide and amonafide against both A549 and HeLa cell lines.

Lineage tracking reveals dynamic relationships of T cells in colorectal cancer.

T cells are key elements of cancer immunotherapy1 but certain fundamental properties, such as the development and migration of T cells within tumours, remain unknown. The enormous T cell receptor (TCR) repertoire, which is required for the recognition of foreign and self-antigens2, could serve as lineage tags to track these T cells in tumours3. Here we obtained transcriptomes of 11,138 single T cells from 12 patients with colorectal cancer, and developed single T cell analysis by RNA sequencing and TCR tracking (STARTRAC) indices to quantitatively analyse the dynamic relationships among 20 identified T cell subsets with distinct functions and clonalities. Although both CD8+ effector and 'exhausted' T cells exhibited high clonal expansion, they were independently connected with tumour-resident CD8+ effector memory cells, implicating a TCR-based fate decision. Of the CD4+ T cells, most tumour-infiltrating T regulatory (Treg) cells showed clonal exclusivity, whereas certain Treg cell clones were developmentally linked to several T helper (TH) cell clones. Notably, we identified two IFNG+ TH1-like cell clusters in tumours that were associated with distinct IFNγ-regulating transcription factors -the GZMK+ effector memory T cells, which were associated with EOMES and RUNX3, and CXCL13+BHLHE40+ TH1-like cell clusters, which were associated with BHLHE40. Only CXCL13+BHLHE40+ TH1-like cells were preferentially enriched in patients with microsatellite-instable tumours, and this might explain their favourable responses to immune-checkpoint blockade. Furthermore, IGFLR1 was highly expressed in both CXCL13+BHLHE40+ TH1-like cells and CD8+ exhausted T cells and possessed co-stimulatory functions. Our integrated STARTRAC analyses provide a powerful approach to dissect the T cell properties in colorectal cancer comprehensively, and could provide insights into the dynamic relationships of T cells in other cancers.

Analysis of the relationship between VEGF, NLRP3 inflammatory complex, EPO levels, and ocular hemodynamics in patients with primary open-angle glaucoma.

OBJECTIVE: Our study aimed to investigate the relationship between vascular endothelial growth factor (VEGF), NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammatory complex, erythropoietin (EPO) levels, and ocular hemodynamics in patients diagnosed with primary open-angle glaucoma (POAG). METHODS: This is a prospective observational study. Patients diagnosed with POAG at The Sixth Hospital of Wuhan hospital between November 2022 and February 2023were enrolled.The patients were categorized into three groups based on the average visual field defect (mean deviation, MD) value: severe injury group (MD > 12 dB, 93 cases), moderate injury group (7 ≤ MD ≤ 12 dB, 89 cases), and mild injury group (MD < 7 dB, 85 cases). The levels of VEGF, NLRP3 inflammatory complex, EPO, and ocular hemodynamics were compared among the groups. Furthermore, the relationship between VEGF, NLRP3, EPO levels, and ocular hemodynamics in patients with POAG was analyzed using Pearson correlation analysis. After adjusting for confounding factors such as age and gender, multivariate Logistic regression analysis was performed with the ocular hemodynamics indexes being used as dependent variables, and VEGF, NLRP3, ASC, Caspase-1, and EPO being used as independent variables. RESULTS: A total of267 patients with POAG were enrolled. There were no significant differences in sex, age, body mass index, systolic blood pressure, diastolic blood pressure, smoking, alcohol consumption, and blood glucose between the two groups (P > 0.05). The levels of NLRP3, ASC, Caspase-1, and EPO in the severe and moderate injury groups were higher than those in the mild injury group, whereas the VEGF levels were lower in the severe and moderate groups compared to the mild group, showing significant differences (P < 0.05). The severe group exhibited higher levels of NLRP3, ASC, Caspase-1, and EPO than the moderate group, while the VEGF levels were lower in the severe group compared to the moderate group, showing significant differences (P < 0.05). The peak systolic velocity(PSV) and resistance index (RI) were higher in the severe and moderate groups than in the mild group, whereas the EDV was significantly lower in the severe and moderate groups compared to the mild group (P < 0.05). The severe group exhibited higher PSV and RI values compared to the moderate group, while the EDV was lower in the severe group compared to the moderate group, showing significant differences (P < 0.05). Pearson correlation analysis was performed to examine the relationship between VEGF, NLRP3, EPO levels, and ocular hemodynamics in patients with POAG. VEGF, NLRP3, ASC, Caspase-1, and EPO showed positive correlations with PSV and RI, and negative correlations with EDV in patients with POAG. Regression analysis showed that VEGF, NLRP3, ASC, Caspase-1 and EPO were significantly correlated with ocular hemodynamics in POAG (all P < 0.001). CONCLUSION: We demonstrated that the levels of VEGF, NLRP3 inflammatory complex, and EPO were highly associated with ocular hemodynamics in patients diagnosed with POAG.

Association between physical activity based on wearables and self-reported health status among adolescents: NHANES 2011-2014.

BACKGROUND: Physical activity (PA) was strongly associated with health status, with fewer related studies in adolescents (12-19 years). Most current studies using questionnaires to assess PA levels were not objective enough. So, this study used a wearable device to assess PA levels quantitatively and focused on the association between PA levels and self-reported 4 health status among adolescents. METHODS: Data were obtained from adolescents (2241) with both PA and health status assessments from two cycles of NHANES, 2011-2014, using a wearable accelerometer-based device to assess PA levels quantitatively, MIMS-units as the metric, averaging over all valid days of wear (MIMS-units average). There were 4 health statuses, including (1) whether or not flu, pneumonia, or ear infection, (2) whether or not stomach or intestinal illness, (3) whether or not head cold or chest cold, and (4) general health condition, from the past 30 days self-reported. Weighted multiple logistic regression was used to analyze the association between the 4 health statuses and the MIMS-units average and MIMS-units average quartiles respectively. Subgroup analyses were also conducted on age, sex, BMI, and race. RESULTS: After controlling confounding factors, there was no significant correlation between the MIMS-units average and the four physical health conditions in Table 3 model 3. While MIMS-units average quartiles results showed that compared to lower PA levels (Q1), higher PA levels (Q4) were linked to a lower incidence of "flu"(OR = 0.94, 95% CI [0.91, 0.99], P < 0.001). Furthermore, Q3 was linked to a decrease in the incidence of "head cold" (OR = 0.91, 95% CI [0.85, 0.96], P < 0.001), while Q2 showed a decrease in "stomach illness" (OR = 0.95, 95% CI [0.92, 0.99], P = 0.003) in Table 3 model 3. Subgroup analyses showed that higher PA levels significantly reduced "flu" risk among 12-15 year-olds, girls, obese, and Non-Hispanic White; decreased "head cold" risk among 16-19 year-olds, boys, obese, and Non-Hispanic White; significantly lower risk of "stomach illness" in girls. CONCLUSIONS: Enhancing PA levels can help prevent flu, head cold, and stomach or intestinal illness in US adolescents. Further studies are needed to determine whether adolescents in other regions have similar results, and high-quality cohort studies are needed to further validate the causal association.

Selective recycling of lithium from spent LiNixCoyMn1-x-yO2 cathode via constructing a synergistic leaching environment.

The global response to lithium scarcity is overstretched, and it is imperative to explore a green process to sustainably and selectively recover lithium from spent lithium-ion battery (LIB) cathodes. This work investigates the distinct leaching behaviors between lithium and transition metals in pure formic acid and the auxiliary effect of acetic acid as a solvent in the leaching reaction. A formic acid-acetic acid (FA-AA) synergistic system was constructed to selectively recycle 96.81% of lithium from spent LIB cathodes by regulating the conditions of the reaction environment to inhibit the leaching of non-target metals. Meanwhile, the transition metals generate carboxylate precipitates enriched in the leaching residue. The inhibition mechanism of manganese leaching by acetic acid and the leaching behavior of nickel or cobalt being precipitated after release was revealed by characterizations such as XPS, SEM, and FTIR. After the reaction, 90.50% of the acid can be recycled by distillation, and small amounts of the residual Li-containing concentrated solution are converted to battery-grade lithium carbonate by roasting and washing (91.62% recovery rate). This recycling process possesses four significant advantages: i) no additional chemicals are required, ii) the lithium sinking step is eliminated, iii) no waste liquid is discharged, and iv) there is the potential for profitability. Overall, this study provides a novel approach to the waste management technology of lithium batteries and sustainable recycling of lithium resources.

Robot-assisted radical nephroureterectomy using the KangDuo Surgical Robot-01 System versus the da Vinci System: a multicenter prospective randomized controlled trial.

INTRODUCTION: We aim to compare the safety and effectiveness of the KangDuo (KD)-Surgical Robot-01 (KD-SR-01) system and the da Vinci (DV) system for robot-assisted radical nephroureterectomy (RARNU). MATERIALS AND METHODS: This multicenter prospective randomized controlled trial was conducted between March 2022 and September 2023. Group 1 included 29 patients undergoing KD-RARNU. Group 2 included 29 patients undergoing DV-RARNU. Patient demographic and clinical characteristics, perioperative data, and follow-up outcomes were collected prospectively and compared between the two groups. RESULTS: There were no significant differences in patient baseline demographic and preoperative characteristics between the two groups. The success rates in both groups were 100% without conversion to open or laparoscopic surgery or positive surgical margins. No significant difference was observed in docking time [242 (120-951) s vs 253 (62-498) s, P = 0.780], console time [137 (55-290) min vs 105 (62-220) min, P = 0.114], operative time [207 (121-460) min vs 185 (96-305) min, P = 0.091], EBL [50 (10-600) mL vs 50 (10-700) mL, P = 0.507], National Aeronautics and Space Administration Task Load Index scores, and postoperative serum creatinine levels between the two groups. None of the patients showed evidence of distant metastasis, local recurrence, or equipment-related adverse events during the four-week follow-up. One (3.4%) patient in Group 2 experienced postoperative enterovaginal and enterovesical fistulas (Clavien-Dindo grade III). CONCLUSIONS: The KD-SR-01 system is safe and effective for RARNU compared to the DV Si or Xi system. Further randomized controlled studies with larger sample sizes and longer durations are required.

New High-Performance Piezoelectric: Ferroelectric Carbon-Boron Clathrate.

High-performance piezoelectrics have been extensively reported with a typical perovskite structure, in which a huge breakthrough in piezoelectric constants is found to be more and more difficult. Hence, the development of materials beyond perovskite is a potential means of achieving lead-free and high piezoelectricity in next-generation piezoelectrics. Here, we demonstrate the possibility of developing high piezoelectricity in the nonperovskite carbon-boron clathrate with the composition of ScB_{3}C_{3} using first-principles calculations. The robust and highly symmetric B-C cage with mobilizable Sc atom constructs a flat potential valley to connect the ferroelectric orthorhombic and rhombohedral structures, which allows an easy, continuous, and strong polarization rotation. By manipulating the cell parameter b, the potential energy surface can be further flattened to produce an extra-high shear piezoelectric constant d_{15} of 9424 pC/N. Our calculations also confirm the effectiveness of the partial chemical replacement of Sc by Y to form a morphotropic phase boundary in the clathrate. The significance of large polarization and high symmetric polyhedron structure is demonstrated for realizing strong polarization rotation, offering the universal physical principles to aid the search for new high-performance piezoelectrics. This work takes ScB_{3}C_{3} as an example to exhibit the great potential for realizing high piezoelectricity in clathrate structure, which opens the door to developing next-generation lead-free piezoelectric applications.

Thermodynamic and Kinetic Behaviors of Persulfate-Based Electron-Transfer Regime in Carbocatalysis.

A carbon-based advanced oxidation process is featured for the nonradical electron-transfer pathway (ETP) from electron-donating organic compounds to activated persulfate complexes, enabling it as a green technology for the selective oxidation of organic pollutants in complex water environments. However, the thermodynamic and kinetic behaviors of the nonradical electron-transfer regime had been ambiguous due to a neglect of the influence of pH on the mechanisms. In this study, three kinds of organic pollutants were divided in the carbon-based ETP regime: (i) physio-adsorption, (ii) adsorption-dominated ETP (oxidation rate slightly surpasses adsorption rate), and (iii) oxidation-dominated ETP (oxidation rate outpaces the adsorption rate). The differential kinetic behaviors were attributed to the physicochemical properties of the organic pollutants. For example, the hydrophobicity, molecular radius, and positive electrostatic potential controlled the mass-transfer process of the adsorption stage of the reactants (peroxydisulfate (PDS) and organics). Meanwhile, other descriptors, including the Fukui index, oxidation potential, and electron cloud density regulated the electron-transfer processes and thus the kinetics of oxidation. Most importantly, the oxidation pathways of these organic pollutants could be altered by adjusting the water chemistry. This study reveals the principles for developing efficient nonradical systems to selectively remove and recycle organic pollutants in wastewater.

Recent advances in micro-sized oxygen carriers inspired by red blood cells.

Supplementing sufficient oxygen to cells is always challenging in biomedical engineering fields such as tissue engineering. Originating from the concept of a 'blood substitute', nano-sized artificial oxygen carriers (AOCs) have been studied for a long time for the optimization of the oxygen supplementation and improvement of hypoxia environments in vitro and in vivo. When circulating in our bodies, micro-sized human red blood cells (hRBCs) feature a high oxygen capacity, a unique biconcave shape, biomechanical and rheological properties, and low frictional surfaces, making them efficient natural oxygen carriers. Inspired by hRBCs, recent studies have focused on evolving different AOCs into microparticles more feasibly able to achieve desired architectures and morphologies and to obtain the corresponding advantages. Recent micro-sized AOCs have been developed into additional categories based on their principal oxygen-carrying or oxygen-releasing materials. Various biomaterials such as lipids, proteins, and polymers have also been used to prepare oxygen carriers owing to their rapid oxygen transfer, high oxygen capacity, excellent colloidal stability, biocompatibility, suitable biodegradability, and long storage. In this review, we concentrated on the fabrication techniques, applied biomaterials, and design considerations of micro-sized AOCs to illustrate the advances in their performances. We also compared certain recent micro-sized AOCs with hRBCs where applicable and appropriate. Furthermore, we discussed existing and potential applications of different types of micro-sized AOCs.

[A Novel Single-arm Single-port Micro-traumatic Laparoscopic Robotic Surgical System].

As the robotic assisted single port surgery arousing attention, a novel single-arm single-port micro-traumatic laparoscopic robotic surgical system is proposed in this study. From the perspective of the mechanics, joints with high rigidity and high reliability were utilized to realize the remote center of motion (RCM). Besides, the cost of consumables was reduced by adding the support of the rigid endoscope. From the perspective of the algorithm, high-precision motion control method and feedback force protection mechanism were implemented. The effectiveness of the aforementioned characteristics were verified by five clinical experiments of cholecystectomy. The results showed that the system is able to reduce the amount of bleeding, accelerate the patient recovery, reduce the infection risk and shorten the learning period. The robotic surgical system had significant clinical application value.

Multiscale diffractive U-Net: a robust all-optical deep learning framework modeled with sampling and skip connections.

As an all-optical learning framework, diffractive deep neural networks (D2NNs) have great potential in running speed, data throughput, and energy consumption. The depth of networks and the misalignment of layers are two problems to limit its further development. In this work, a robust all-optical network framework (multiscale diffractive U-Net, MDUNet) based on multi-scale features fusion has been proposed. The depth expansion and alignment robustness of the network can be significantly improved by introducing sampling and skip connections. Compared with common all-optical learning frameworks, MDUNet achieves the highest accuracy of 98.81% and 89.11% on MNIST and Fashion-MNIST respectively. The testing accuracy of MNIST and Fashion-MNIST can be further improved to 99.06% and 89.86% respectively by using the ensemble learning method to construct the optoelectronic hybrid neural network.

Perspective of fibre-optical microendoscopy with microlenses.

Fibre-optical microendoscopy is based on fibre-optical confocal scanning microscopy, where optical fibres are introduced for delivery of the source and collection of the signal. Fibre-optical microendoscopy has led to innovations in imaging of freely moving animals, long-term imaging, minimally invasive diagnostics, and microsurgery. The lens system in fibre-optical microendoscopy is significant because of the imaging resolution and miniaturisation possibility. State-of-the-art fibre-optical microendoscopy based on various types of lens systems is introduced and compared. The lens system contains an objective lens, a gradient index microlens, and other novel lens systems fabricated by electric arc discharge or two-photon lithography.

Optical fibres are introduced in confocal scanning microscopy, inspiring the development of fibre-optical microendoscopy. Fibre-optical microendoscopy takes advantages in imaging of freely moving animals, long-term imaging, minimally invasive diagnostics, and microsurgery. The lens system helps resolving small details of samples and reducing the size in a fibre-optical microendoscope. Various types of lens systems applied in the fibre-optical microendoscopes are introduced and compared, including an objective lens, a gradient index microlens, and other nanofabricated microlens systems.

Gut Microbial Divergence Between Three Hadal Amphipod Species from the Isolated Hadal Trenches.

Amphipods are the dominant scavenging metazoan species in the hadal trenches at water depths below 6,000 m. The gut microbiota have been considered to be contribution to the adaptation of deep-sea organisms; however, few comparative analyses of animal gut microbiota between different isolated hadal environments have been done so far. Here, we employed high-throughput 16S rRNA sequencing to compare the gut microbial taxonomic composition and functional potential diversity of three hadal amphipod species, Hirondellea gigas, Bathycallisoma schellenbergi, and Alicella gigantea, collected from the Mariana Trench, Marceau Trench, and New Britain Trench in the Pacific Ocean, respectively. Results showed that different community compositions were detected across all the amphipod specimens based on the analyses of alpha-diversity, hierarchical cluster tree, and PCoA (principal coordinate analysis). Moreover, almost no correlation was observed between genera overrepresented in different amphipods by microbe-microbe correlations analysis, which suggested that the colonization of symbionts were host-specific. At genus level, Psychromonas was dominant in H. gigas, and Candidatus Hepatoplasma was overall dominant in A. gigantea and B. schellenbergi. Comparison of the functional potential showed that, though three hadal amphipod species shared the same predominant functional pathways, the abundances of those most shared pathways showed distinct differences across all the specimens. These findings pointed to the enrichment of particular functional pathways in the gut microbiota of the different isolated trench amphipods. Moreover, in terms of species relative abundance, alpha-diversity and beta-diversity, there was high similarity of gut microbiota between the two A. gigantea populations, which dwelled in two different localities of the same hadal trench. Altogether, this study provides an initial investigation into the gut-microbial interactions and evolution at the hadal depths within amphipod. Each of these three amphipod species would be a model taxa for future studies investigating the influence habitat difference and geography on gut-microbial communities.

The putative obtusifoliol 14α-demethylase OsCYP51H3 affects multiple aspects of rice growth and development.

Some members of the CYP51G subfamily has been shown to be obtusifoliol 14α-demethylase, key enzyme of the sterol and brassinosteroid (BR) biosynthesis, which mediate plant development and response to stresses. However, little is known about the functions of CYP51H subfamily in rice. Here, OsCYP51H3, an ortholog of rice OsCYP51G1 was identified. Compared with wild type, the mutants oscyp51H3 and OsCYP51H3-RNAi showed dwarf phenotype, late flowering, erected leaves, lower seed-setting rate, and smaller and shorter seeds. In contrast, the phenotypic changes of OsCYP51H3-OE plants are not obvious. Metabolomic analysis of oscyp51H3 mutant indicated that OsCYP51H3 may also encode an obtusifoliol 14α-demethylase involved in phytosterol and BR biosynthesis, but possibly not that of triterpenes. The RNA-seq results showed that OsCYP51H3 may affect the expression of a lot of genes related to rice development. These findings showed that OsCYP51H3 codes for a putative obtusifoliol 14α-demethylase involved in phytosterol and BR biosynthesis, and mediates rice development.

Electro-Induced Carbon Nanotube Discrete Electrodes for Sustainable Persulfate Activation.

In electrochemical advanced oxidation processes (EAOPs), the rate-limiting step is the mass transfer of pollutants to the electrodes due to the limited active surface areas. To this end, we established a three-dimensional (3D) EAOP system by coupling conventional graphite electrodes with dispersed carbon nanotubes (CNTs). The electrodes (particularly the anode) induced electric field spontaneously polarized CNTs into dispersed reactive particle electrodes (CNT-PEs) in the solution, which remarkably promoted electrochemical activation of peroxydisulfate (PDS) to generate surface CNT-PDS* complexes and surface-bound radicals (SBRs). Based on the excited potential (ECNT-PEs) at different positions in the 3D electric field, CNT-PEs were activated into three states. (i) ECNT-PEs < Eorganic, CNT-PEs are chemically inert toward DCP oxidation; (ii) Eorganic < ECNT-PEs < Ewater, CNT-PEs will oxidize DCP via an electron-transfer process (ETP); (iii) ECNT-PEs > Ewater, both CNT-PDS* complexes and the anode will oxidize water to produce SBRs. Thus, DCP could be oxidized by CNT-PDS* complexes via ETP to form polychlorophenols on the CNT surface, causing rapid deactivation of the micro-electrodes. In contrast, SBRs attack DCP directly into chloride ions and hydroxylated products, maintaining the surface cleanliness and activity of CNT-PEs for long-term operations.

Synthesis and biological evaluation of aminobenzamides containing purine moiety as class I histone deacetylases inhibitors.

The aminobenzamide is selective to class I histone deacetylases (HDACs) and displays unique tight-binding/slow-off HDAC-binding mechanism. Herein, we report a series of 9-substituted purine aminobenzamides that selectively inhibit class I HDACs. The activities in vitro showed compound 9d exhibited 12 folds more potent than MS-275 against HDAC1 isoform and showed excellent inhibitory activity on cancer cells, including HCT-116, MDA-MB-231, K562 cell lines. The metabolic stability of 9d was much better than that of the well-known HDAC inhibitor SAHA. Pulse exposure test of western blot assay demonstrated that 9a, 9d induced histone acetylation in a similar manner to MS-275. Further biological validation demonstrated that 9d prevented cell transition from G1 phase to S phase by reducing Cyclin D1, CDK2 and lifting p21, induced early apoptosis by upregulating BAX and downregulating Bcl-2 in HCT-116 cells.