Genome-wide distribution of 5-hydroxymethyluracil and chromatin accessibility in the Breviolum minutum genome.

BACKGROUND: In dinoflagellates, a unique and extremely divergent genomic and nuclear organization has evolved. The highly unusual features of dinoflagellate nuclei and genomes include permanently condensed liquid crystalline chromosomes, primarily packaged by proteins other than histones, genes organized in very long unidirectional gene arrays, a general absence of transcriptional regulation, high abundance of the otherwise very rare DNA modification 5-hydroxymethyluracil (5-hmU), and many others. While most of these fascinating properties are originally identified in the 1970s and 1980s, they have not yet been investigated using modern genomic tools. RESULTS: In this work, we address some of the outstanding questions regarding dinoflagellate genome organization by mapping the genome-wide distribution of 5-hmU (using both immunoprecipitation-based and basepair-resolution chemical mapping approaches) and of chromatin accessibility in the genome of the Symbiodiniaceae dinoflagellate Breviolum minutum. We find that the 5-hmU modification is preferentially enriched over certain classes of repetitive elements, often coincides with the boundaries between gene arrays, and is generally correlated with decreased chromatin accessibility, the latter otherwise being largely uniform along the genome. We discuss the potential roles of 5-hmU in the functional organization of dinoflagellate genomes and its relationship to the transcriptional landscape of gene arrays. CONCLUSIONS: Our results provide the first window into the 5-hmU and chromatin accessibility landscapes in dinoflagellates.

Enhancing activity and stability of FeNC catalysts through co incorporation for oxygen reduction reaction.

FeNC single atom catalysts (SACs) have attracted great interest due to their highly active FeN4 sites. However, the pyrolysis treatment often leads to inevitable metal migration and aggregation, which reduces the catalytic activity. Moreover, due to the Fenton reaction caused by FeNC in alkaline and acidic solutions, the presence of Fe and peroxide in electrodes may generate free radicals, resulting in serious degradation of the organic ionomer and the membrane. Herein, we report an original strategy of introducing Co single atoms into FeNC catalysts, forming atomically dispersed bimetallic active sites (FeCoNC) and improving the activity and stability of the catalyst. Benefiting from this strategy, FeCoNC catalyst exhibits excellent oxygen reduction reaction (ORR) activity in alkaline media (E1/2 = 0.88 V) and in acidic media (E1/2 = 0.77 V). As the cathode of Zn-air battery (ZAB), FeCoNC shows an excellent peak power density of 142.8 mW cm-2 and a specific capacity of 806.6 mAh/gZn. This work provides a novel avenue to optimize and enhance the ORR performance of atomic dispersed FeNC catalysts.

Biosynthesis of chlorophyll c in a dinoflagellate and heterologous production in planta.

Chlorophyll c is a key photosynthetic pigment that has been used historically to classify eukaryotic algae. Despite its importance in global photosynthetic productivity, the pathway for its biosynthesis has remained elusive. Here we define the CHLOROPHYLL C SYNTHASE (CHLCS) discovered through investigation of a dinoflagellate mutant deficient in chlorophyll c. CHLCSs are proteins with chlorophyll a/b binding and 2-oxoglutarate-Fe(II) dioxygenase (2OGD) domains found in peridinin-containing dinoflagellates; other chlorophyll c-containing algae utilize enzymes with only the 2OGD domain or an unknown synthase to produce chlorophyll c. 2OGD-containing synthases across dinoflagellate, diatom, cryptophyte, and haptophyte lineages form a monophyletic group, 8 members of which were also shown to produce chlorophyll c. Chlorophyll c1 to c2 ratios in marine algae are dictated in part by chlorophyll c synthases. CHLCS heterologously expressed in planta results in the accumulation of chlorophyll c1 and c2, demonstrating a path to augment plant pigment composition with algal counterparts.

Super-enhancer-associated EEPD1 facilitates EMT-mediated metastasis by regulating the PI3K/AKT/mTOR pathway in gastric cancer.

This study focused on exploring the mechanism of the EMT mediated by endonuclease/exonuclease/phosphatase family domain-containing 1 (EEPD1) in gastric cancer metastasis. Through bioinformatics analysis, EEPD1 was found to be a target gene of super enhancers (SEs) in gastric cancer tissues. EEPD1 exhibited higher expression levels in tumor tissues and was associated with poor prognosis. In vitro and in vivo studies have demonstrated that silencing EEPD1 significantly suppressed the proliferation, metastasis, and invasion of gastric cancer cells. Furthermore, EEPD1 knockdown was involved in the regulation of the EMT and suppressed expression of AKT, a downstream component of the PI3K pathway, leading to a reduction in the phosphorylation levels of AKT and its downstream molecule, mTOR. These results showed the potential of EEPD1 as a prognostic indicator and therapeutic target in gastric cancer.

Genome-wide distribution of 5-hydroxymethyluracil and chromatin accessibility in the Breviolum minutum genome.

In dinoflagellates, a unique and extremely divergent genomic and nuclear organization has evolved. The highly unusual features of dinoflagellate nuclei and genomes include permanently condensed liquid crystalline chromosomes, primarily packaged by proteins other than histones, genes organized in very long unidirectional gene arrays, a general absence of transcriptional regulation, high abundance of the otherwise very rare DNA modification 5-hydroxymethyluracil (5-hmU), and many others. While most of these fascinating properties were originally identified in the 1970s and 1980s, they have not yet been investigated using modern genomic tools. In this work, we address some of the outstanding questions regarding dinoflagellate genome organization by mapping the genome-wide distribution of 5-hmU (using both immunoprecipitation-based and basepair-resolution chemical mapping approaches) and of chromatin accessibility in the genome of the Symbiodiniaceae dinoflagellate Breviolum minutum. We find that the 5-hmU modification is preferentially enriched over certain classes of repetitive elements, often coincides with the boundaries between gene arrays, and is generally correlated with decreased chromatin accessibility, the latter otherwise being largely uniform along the genome. We discuss the potential roles of 5-hmU in the functional organization of dinoflagellate genomes and its relationship to the transcriptional landscape of gene arrays.

Protocol for the generation of Symbiodiniaceae mutants using UV mutagenesis.

Genetic approaches are limited in the dinoflagellate family, Symbiodiniaceae, causing a bottleneck in the discovery of useful mutants toward the goal of preventing future coral bleaching events. In this protocol, we demonstrate the application of UV exposure, coupled with downstream phenotypic screening and mutant isolation, to form a UV mutagenesis pipeline. This pipeline provides an avenue to generate Symbiodiniaceae mutants to help link genotype to phenotype, as well as address previously unanswered questions surrounding relationships with host organisms, like coral. For complete details on the use and execution of this protocol, please refer to Jinkerson et al. (2022).1.

A TTFS-based energy and utilization efficient neuromorphic CNN accelerator.

Spiking neural networks (SNNs), which are a form of neuromorphic, brain-inspired AI, have the potential to be a power-efficient alternative to artificial neural networks (ANNs). Spikes that occur in SNN systems, also known as activations, tend to be extremely sparse, and low in number. This minimizes the number of data accesses typically needed for processing. In addition, SNN systems are typically designed to use addition operations which consume much less energy than the typical multiply and accumulate operations used in DNN systems. The vast majority of neuromorphic hardware designs support rate-based SNNs, where the information is encoded by spike rates. Generally, rate-based SNNs can be inefficient as a large number of spikes will be transmitted and processed during inference. One coding scheme that has the potential to improve efficiency is the time-to-first-spike (TTFS) coding, where the information isn't presented through the frequency of spikes, but instead through the relative spike arrival time. In TTFS-based SNNs, each neuron can only spike once during the entire inference process, and this results in high sparsity. The activation sparsity of TTFS-based SNNs is higher than rate-based SNNs, but TTFS-based SNNs have yet to achieve the same accuracy as rate-based SNNs. In this work, we propose two key improvements for TTFS-based SNN systems: (1) a novel optimization algorithm to improve the accuracy of TTFS-based SNNs and (2) a novel hardware accelerator for TTFS-based SNNs that uses a scalable and low-power design. Our work in TTFS coding and training improves the accuracy of TTFS-based SNNs to achieve state-of-the-art results on the MNIST and Fashion-MNIST datasets. Meanwhile, our work reduces the power consumption by at least 2.4×, 25.9×, and 38.4× over the state-of-the-art neuromorphic hardware on MNIST, Fashion-MNIST, and CIFAR10, respectively.

Nanoreactor of Fe, N Co-Doped Hollow Carbon Spheres for Oxygen Reduction Catalysis.

A simple template strategy was applied to prepare a Fe, N co-doped hollow carbon (Fe-NHC) nanoreactor for the oxygen reduction reaction (ORR) by coating Fe nanoparticles (Fe-NPs) with polydopamine (PDA), followed by high temperature pyrolysis and acid-leaching. With this method, Fe-NPs were used as both the template and the metal precursor, so that the nanoreactors can preserve the original spherical morphology and embed Fe single atoms on the inner walls. The carbonized PDA contained abundant N content, offering an ideal coordination environment for Fe atoms. By regulating the mass ratio of Fe-NPs and PDA, an optimal sample with a carbon layer thickness of 12 nm (Fe-NHC-3) was obtained. The hollow spherical structure of the nanoreactors and the atomically dispersed Fe were verified by various physical characterizations. As a result, Fe-NHC-3 performed well in ORR tests under alkaline conditions, with high catalytic activity, durability, and methanol resistance, demonstrating that the as-fabricated materials have the potential to be applied in the cathodic catalysis of fuel cells.

Characterization and comprehensive evaluation of phenotypic characters in wild Camellia oleifera germplasm for conservation and breeding.

Camellia oleifera Abel. is an economically important woody oil plant native to China. To explore the genetic diversity of wild C. oleifera phenotypic traits and effectively protect these germplasm resources, this study provides a thorough evaluation of the phenotypic variability of a cluster of 143 wild C. oleifera germplasm resources. A total of 41 characters, including leaves, flowers, fruits, seeds, and oil quality characters, were investigated based on the quantization of physical and chemical descriptors and digital image analysis. The findings revealed significant variations among the 41 characters with a high range of Shannon-Wiener indexes (H') from 0.07 to 2.19. The coefficient of variation (CV) among 32 quantitative characters ranged from 5.34% to 81.31%, with an average of 27.14%. High genetic diversity was also detected among the 143 germplasm. Based on the analysis of hierarchical clustering, 143 accessions were separated into six categories. All the individuals can be clearly distinguished from each other according to the result of the principal component analysis (PCA). The M-TOPSIS exhaustive evaluation method based on correlation and PCA analyses of 32 quantitative characters was applied for the 143 wild C. oleifera accessions, and the top 10 varieties were identified as YA53, YA13, YA40, YA34, YA57, YA19, YA33, YA41, DZ8, and YA7. This research optimized the germplasm evaluation system and perfected the statistical phenotypic traits for distinctness, uniformity, and stability (DUS) testing. Some top-notch germplasm sources were also screened for oil-tea Camellia breeding.

Safe engineering of cancer-associated fibroblasts enhances checkpoint blockade immunotherapy.

Abundant cancer-associated fibroblasts (CAFs) in highly fibrotic breast cancer constitute an immunosuppressive barrier for T cell activity and are closely related to the failure of immune checkpoint blockade therapy (ICB). Inspired by the similar antigen-processing capacity of CAFs to professional antigen-presenting cells (APCs), a "turning foes to friends" strategy is proposed by in situ engineering immune-suppressed CAFs into immune-activated APCs for improving response rates of ICB. To achieve safe and specific CAFs engineering in vivo, a thermochromic spatiotemporal photo-controlled gene expression nanosystem was developed by self-assembly of molten eutectic mixture, chitosan andfusion plasmid. After photoactivatable gene expression, CAFs could be engineered as APCs via co-stimulatory molecule (CD86) expression, which effectively induced activation and proliferation of antigen-specific CD8 + T cells. Meanwhile, engineered CAFs could also secrete PD-L1 trap protein in situ for ICB, avoiding potential autoimmune-like disorders caused by "off-target" effects of clinically applied PD-L1 antibody. The study demonstrated that the designed nanosystem could efficiently engineer CAFs, significantly enhance the percentages of CD8+ T cells (4-folds), result in about 85% tumor inhibition rate and 83.3% survival rate at 60 days in highly fibrotic breast cancer, further inducing long-term immune memory effects and effectively inhibiting lung metastasis.

Microplastics stimulated nitrous oxide emissions primarily through denitrification: A meta-analysis.

Microplastics can profoundly alter nitrogen cycling. However, it remains poorly understood how microplastics impact soil nitrogen processes and generate N2O. A meta-analysis was conducted for this investigation based on 60 published studies to elucidate the effects of microplastics on soil nitrogen cycling, from genes to processes. Under microplastic exposure, the emissions of soil N2O was significantly increased (140.6%), while the nitrate reductase activities increased by 4.8%. The denitrification rate and number of denitrifier genes were increased by 17.8% and 10.6%, respectively. Meanwhile, the nitrification rate and nitrifier genes were not significantly altered, so did the nitrogen immobilization and mineralization rates. The additional emission of soil N2O might primarily from stimulated denitrification. Soil N2O emission and denitrification genes were always increased, regardless of the concentrations of microplastic or experiment duration. As a result, the nitrite was increased by 38.8% and nitrate was decreased by 22.4%, respectively. Interestingly, the N2O emission increments and copy number of denitrifiers genes diminished over time. This study revealed divergent changes in soil nitrogen processes and highlighted N2O emissions with a greater denitrification rate under microplastic exposure. The negative impacts of microplastics on soil health were revealed from the perspective of soil nitrogen availability and N2O emissions.

Research progress of bacterial flagellin as a vaccine adjuvant / 中国生物制品学杂志

@#Vaccines play an important role in the prevention and control of infectious diseases. Bacterial flagellin can activate Toll like receptor 5(TLR5) and NOD like receptor C4(NLRC4) in host cells,and has immune adjuvant effect. As a new immune adjuvant,flagellin can not only share with antigen protein,but also fuse with antigen protein,which can significantly improve the immune effect. At the same time,it has achieved good application effect in mucosal immunity and antitumor immunity,becoming a hot spot in the research and development of vaccine adjuvants. This review mainly discussed the research progress on application of bacterial flagellin as vaccine adjuvant,so as to provide new ideas for the development of flagellin adjuvant vaccine.

Secondary-Heteroatom-Doping-Derived Synthesis of N, S Co-Doped Graphene Nanoribbons for Enhanced Oxygen Reduction Activity.

The rareness and weak durability of Pt-based electrocatalysts for oxygen reduction reactions (ORRs) have hindered the large-scale application of fuel cells. Here, we developed an efficient metal-free catalyst consisting of N, S co-doped graphene nanoribbons (N, S-GNR-2s) for ORRs. GNRs were firstly synthesized via the chemical unzipping of carbon nanotubes, and then N, S co-doping was conducted using urea as the primary and sulfourea as the secondary heteroatom sources. The successful incorporation of nitrogen and sulfur was confirmed by elemental mapping analysis as well as X-ray photoelectron spectroscopy. Electrochemical testing revealed that N, S-GNR-2s exhibited an Eonset of 0.89 V, E1/2 of 0.79 V and an average electron transfer number of 3.72, as well as good stability and methanol tolerance. As a result, N, S-GNR-2s displayed better ORR property than either N-GNRs or N, S-GNRs, the control samples prepared with only a primary heteroatom source, strongly clarifying the significance of secondary-heteroatom-doping on enhancing the catalytic activity of carbon-based nanomaterials.

Reproducible propagation technique for the symbiotic cnidarian model system Cassiopea xamachana.

The phylum Cnidaria is composed of corals, jellyfish, hydras, and sea anemones. Cnidarians are well-known for their regenerative capability, with many species maintaining the ability to regenerate complete structures. This regenerative capacity has been used casually for propagation purposes (via dissection) for some cnidarians used in laboratory research but has yet been documented in a manner meant to be reproducible. One such cnidarian model system is the scyphozoan jellyfish Cassiopea xamachana. C. xamachana has become an emerging model system for studying the cnidarian-algal symbiotic relationship, so determining a reliable and fast method for expansion of laboratory animals is crucial. Here we outline a reproducible propagation method for continued generation and growth of C. xamachana polyps. This article has an associated First Person interview with the first author of the paper.

Inhibition of NLRC5 attenuates the malignant growth and enhances the sensitivity of gastric cancer cells to 5-FU chemotherapy by blocking the carcinogenic effect of YY1.

Gastric cancer (GC) is one of the commonest malignant tumors of the digestive system, characterized by high morbidity and mortality rates. It has been reported that NOD like receptor (NLR) family, CARD domain containing 5 (NLRC5) serves an important role in the occurrence and development of GC. Therefore, the current study aimed to investigate the role of NLRC5 in GC. The mRNA and protein expression levels of NLRC5 in GC cell lines were determined by reverse transcription-quantitative PCR and western blot analysis, respectively. Additionally, following NLRC5 knockdown, cell proliferation, invasion and migration were evaluated using Cell Counting Kit 8, colony formation, wound healing and Transwell assays, and western blot analysis. The NLRC and Yin Yang 1 (YY1) expression in the AGS cells with 5-FU resistance were detected by western blotting. The sensitivity of GC cells to 5-fluorouracil (5-FU) was detected by flow cytometry and western blot analysis. Additionally, the binding capacity of YY1 on NLRC5 promoter was predicted using JASPAR database and it was further verified by chromatin immunoprecipitation and luciferase reporter assays. Finally, to elucidate the mechanism underlying the effect of NLRC5 on GC, YY1 was overexpressed and NLRC5 was silenced in GC cell lines. The results showed that NLRC5 was abnormally upregulated in GC cells. In addition, NLRC5 knockdown significantly attenuated the proliferation, invasion and migration abilities of GC cells, while it enhanced the sensitivity of GC cells to 5-FU. The above effects were regulated by the YY1 transcription factor. Overall, the results of the present study indicated that NLRC5 silencing could reduce the malignant growth and enhance the sensitivity of GC cells to 5-FU chemotherapy via inhibiting the carcinogenic effect of YY1.

Mediating Effect of Self-Efficacy on the Relationship Between Perceived Social Support and Resilience in Patients with Recurrent Schizophrenia in China.

Purpose: To explore the mediating effect of self-efficacy on the relationship between perceived social support and resilience in patients with recurrent schizophrenia in China. Patients and Methods: In this cross-sectional study, a total of 176 patients with recurrent schizophrenia who were hospitalized in a tertiary hospital in Hunan Province, China, completed a general data questionnaire, the Connor Davidson Resilience Scale (CD-RISC), the Perceived Social Support Scale (PSSS) and the General Self-Efficacy Energy Scale (GSES). Results: Among the 176 patients, the mean GSES score was 2.02±0.61, the mean PSSS score was 56.77±14.61, and the mean CD-RISC score was 58.06±17.26. Self-efficacy played a partial mediating role between social support and resilience, and the mediating effect accounted for 42.56% of the total effect. Conclusion: The resilience level of patients with recurrent schizophrenia in China is moderate and needs to be improved. This research revealed that self-efficacy played a part in mediating perceived social support and resilience in patients with recurrent schizophrenia in China. Perceived social support can indirectly affect resilience in patients with recurrent schizophrenia through self-efficacy. Comprehensive interventions in perceived social support and self-efficacy would help to improve the resilience of patients with recurrent schizophrenia.

Copper-based metal-organic framework impedes triple-negative breast cancer metastasis via local estrogen deprivation and platelets blockade.

Metastasis is one of the main causes of failure in the treatment of triple-negative breast cancer (TNBC). Abnormally estrogen level and activated platelets are the key driving forces for TNBC metastasis. Herein, an "ion/gas" bioactive nanogenerator (termed as IGBN), comprising a copper-based MOF and loaded cisplatin-arginine (Pt-Arg) prodrug is developed for metastasis-promoting tumor microenvironment reprogramming and TNBC therapy. The copper-based MOF not only serves as a drug carrier, but also specifically produces Cu2+ in tumors, which catalytic oxidizing estrogen to reduce estrogen levels in situ. Meanwhile, the rationally designed Pt-Arg prodrug reduced into cisplatin to significantly promote the generation of H2O2 in the tumor, then permitting self-augmented cascade NO gas generation by oxidizing Arg through a H2O2 self-supplied way, thus blocking platelet activation in tumor. We clarified that IGBN inhibited TNBC metastasis through local estrogen deprivation and platelets blockade, affording 88.4% inhibition of pulmonary metastasis in a 4T1 mammary adenocarcinoma model. Notably, the locally copper ion interference, NO gas therapy and cisplatin chemotherapy together resulted in an enhanced therapeutic efficacy in primary tumor ablation without significant toxicity. This "ion/gas" bioactive nanogenerator offers a robust and safe strategy for TNBC therapy.

Cnidarian-Symbiodiniaceae symbiosis establishment is independent of photosynthesis.

Photosynthesis shapes the symbiotic relationships between cnidarians and Symbiodiniaceae algae-with many cnidarian hosts requiring symbiont photosynthate for survival-but little is known about how photosynthesis impacts symbiosis establishment. Here, we show that during symbiosis establishment, infection, proliferation, and maintenance can proceed without photosynthesis, but the ability to do so is dependent on specific cnidarian-Symbiodiniaceae relationships. The evaluation of 31 pairs of symbiotic relationships (five species of Symbiodiniaceae in sea anemone, coral, and jellyfish hosts) revealed that infection can occur without photosynthesis. A UV mutagenesis method for Symbiodiniaceae was established and used to generate six photosynthetic mutants that can infect these hosts. Without photosynthesis, Symbiodiniaceae cannot proliferate in the sea anemone Aiptasia or jellyfish Cassiopea but can proliferate in the juvenile polyps of the coral Acropora. After 6 months of darkness, Breviolum minutum is maintained within Aiptasia, indicating that Symbiodiniaceae maintenance can be independent of photosynthesis. Manipulating photosynthesis provides insights into cnidarian-Symbiodiniaceae symbiosis.

Single-cell dissociation of the model cnidarian sea anemone Exaiptasia diaphana.

The sea anemone Exaiptasia diaphana (Aiptasia) is a versatile model in studying cellular mechanisms that govern cnidarian-Symbiodiniaceae symbiosis, the foundation of coral reef ecosystems. Here, we provide a protocol to efficiently dissociate adult Aiptasia tissue into a single-cell suspension using enzymatic digestion. We detail steps including washing animals, dissociating tissue with pronase digestion, and evaluating dissociated single cells using fluorescence imaging. This procedure can be applied to other cnidarians, including coral polyps. For complete details on the use and execution of this protocol, please refer to Jinkerson et al. (2022).1.

The synergistic effect of carbon edges and dopants towards efficient oxygen reduction reaction.

Decoration with alien atoms and increasing the edge content are two valid ways to activate the oxygen reduction reaction (ORR) property of nanocarbons. To further enhance their intrinsic activity and explore the underlying ORR mechanism, graphene nanoribbons (GNRs) were selected as an ideal catalyst model. Theoretical simulations have predicted that with the synergistic effect between heteroatom-doping and edge sites, the ORR activity can be significantly improved. Inspired by this, N-GNRs were synthesized via the oxidative unzipping of CNTs followed by nitrogen incorporation with urea. Ample edges and nitrogen doping sites were detected by high-resolution transmission electron microscopy and X-ray photoelectron spectroscopy, respectively. As a result, N-GNRs exhibited remarkably higher ORR properties in terms of onset and half-wave potentials, Tafel slopes, electron transfer number and methanol tolerance than either GNRs, the control sample without doping, or N-CNTs, the control sample without abundant edges, simply clarifying the significance of synergy between dopants and edges. Thus, this work provides a simple but efficient strategy to fabricate high-performance oxygen reduction catalysts.