GPMeta: a GPU-accelerated method for ultrarapid pathogen identification from metagenomic sequences.

Metagenomic sequencing (mNGS) is a powerful diagnostic tool to detect causative pathogens in clinical microbiological testing owing to its unbiasedness and substantially reduced costs. Rapid and accurate classification of metagenomic sequences is a critical procedure for pathogen identification in dry-lab step of mNGS test. However, clinical practices of the testing technology are hampered by the challenge of classifying sequences within a clinically relevant timeframe. Here, we present GPMeta, a novel GPU-accelerated approach to ultrarapid pathogen identification from complex mNGS data, allowing users to bypass this limitation. Using mock microbial community datasets and public real metagenomic sequencing datasets from clinical samples, we show that GPMeta has not only higher accuracy but also significantly higher speed than existing state-of-the-art tools such as Bowtie2, Bwa, Kraken2 and Centrifuge. Furthermore, GPMeta offers GPMetaC clustering algorithm, a statistical model for clustering and rescoring ambiguous alignments to improve the discrimination of highly homologous sequences from microbial genomes with average nucleotide identity >95%. GPMetaC exhibits higher precision and recall rate than others. GPMeta underlines its key role in the development of the mNGS test in infectious diseases that require rapid turnaround times. Further study will discern how to best and easily integrate GPMeta into routine clinical practices. GPMeta is freely accessible to non-commercial users at https://github.com/Bgi-LUSH/GPMeta.

A Dual-Active Covalent Triazine Framework Film for Efficient Visible-Light-Driven Hydrogen Peroxide Production.

Photocatalytic hydrogen peroxide production from water and oxygen offers a clean and sustainable alternative to the conventional energy-intensive anthraquinone oxidation method. Compared to powdered covalent triazine frameworks (CTFs), the film morphology of CTFs provides better connectivity in 2D, yielding several advantages: more efficient connections between active sites, reduced electron-hole pair recombination, increased resistance to superoxide radical induced corrosion, and decreased light scattering. Leveraging these benefits, it has incorporated dual active sites for both the oxygen reduction reaction (ORR) and the water oxidation reaction (WOR) into a CTF film system. This dual-active CTF film demonstrated an exceptional hydrogen peroxide production rate of 19 460 µmol h⁻¹ m⁻2 after 1 h and 17 830 µmol h⁻¹ m⁻2 after 5 h under visible light irradiation (≥420 nm) without the need for sacrificial agents.

Exosomes regulate SIRT3-related autophagy by delivering miR-421 to regulate macrophage polarization and participate in OSA-related NAFLD.

PURPOSE: To analyze the role of and mechanism underlying obstructive sleep apnea (OSA)-derived exosomes in inducing non-alcoholic fatty liver (NAFLD). METHODS: The role of OSA-derived exosomes was analyzed in inducing hepatocyte fat accumulation in mice models both in vivo and in vitro. RESULTS: OSA-derived exosomes caused fat accumulation and macrophage activation in the liver tissue. These exosomes promoted fat accumulation; steatosis was more noticeable in the presence of macrophages. Macrophages could internalize OSA-derived exosomes, which promoted macrophage polarization to the M1 type. Moreover, it inhibited sirtuin-3 (SIRT3)/AMP-activated protein kinase (AMPK) and autophagy and promoted the activation of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasomes. The use of 3-methyladenine (3-MA) to inhibit autophagy blocked NLRP3 inflammasome activation and inhibited the M1 polarization of macrophages. miR-421 targeting inhibited SIRT3 protein expression in the macrophages. miR-421 was significantly increased in OSA-derived exosomes. Additionally, miR-421 levels were increased in OSA + NAFLD mice- and patient-derived exosomes. In the liver tissues of OSA and OSA + NAFLD mice, miR-421 displayed similar co-localization with the macrophages. Intermittent hypoxia-induced hepatocytes deliver miR-421 to the macrophages via exosomes to inhibit SIRT3, thereby participating in macrophage M1 polarization. After OSA and NAFLD modeling in miR-421-/- mice, liver steatosis and M1 polarization were significantly reduced. Additionally, in the case of miR-421 knockout, the inhibitory effects of OSA-derived exosomes on SIRT3 and autophagy were significantly alleviated. Furthermore, their effects on liver steatosis and macrophage M1 polarization were significantly reduced. CONCLUSIONS: OSA promotes the delivery of miR-421 from the hepatocytes to macrophages. Additionally, it promotes M1 polarization by regulating the SIRT3/AMPK-autophagy pathway, thereby causing NAFLD.

Risk factors of electrical status epilepticus during sleep in children with benign childhood epilepsy with centro-temporal spikes.

Objective: To explore risk factors of electrical status epilepticus during sleep in children with benign childhood epilepsy with centro-temporal spikes (BECT). Methods: This is a clinical comparative study. The subjects of study were 67 children with BECT from the Outpatient Department of Pediatric Neurology in Xingtai People's Hospital from January 2019 to January 2022. According to the occurrence of ESES, the enrolled children were divided into control group which included BECT children without ESES and the observation group which included BECT children with ESES. Compared differences of the two groups in the age of first seizure, the frequency of seizures before treatment, the classification of treatment drugs, cranial MRI, and discharge side of electroencephalogram (EEG). Results: There was no statistical difference between the two groups in the frequency of seizures before treatment, the classification of treatment drugs, cranial MRI, and the distribution of EEG discharges in the left and right cerebral areas(P>0.05). Statistical differences were observed in the age of the first seizure, whether the seizures occurred after treatment, and EEG discharges in unilateral/bilateral cerebral areas (P<0.05). Furthermore, the collinearity test and Logistic regression analysis showed that the age of the first seizure, the frequency of seizures before treatment, and whether the seizures occurred after treatment were independent risk factors for the occurrence of ESES in BECT (P<0.05). Conclusion: Clinically, the occurrence of ESES in children with BECT may be related to the younger age of the first seizure, higher frequency of seizures before treatment, and the occurrence of seizures after treatment.

Precisely Constructing Molecular Junctions in Hydrogen-Bonded Organic Frameworks for Efficient Artificial Photosynthetic CO2 Reduction.

The development of artificial photocatalysts to convert CO2 into renewable fuels and H2O into O2 is a complex and crucial task in the field of photosynthesis research. The current challenge is to enhance photogenerated charge separation, as well as to increase the oxidation capability of materials. Herein, a molecular junction-type porphyrin-based crystalline photocatalyst (Ni-TCPP-TPyP) was successfully self-assembled by incorporating a nickel porphyrin complex as a reduction site and pyridyl porphyrin as an oxidation site via hydrogen bonding and π-π stacking interactions. The resulting material has a highly crystalline structure, and the formation of inherent molecular junctions can accelerate photogenerated charge separation and transport. Thus, Ni-TCPP-TPyP achieved an excellent CO production rate of 309.3 µmol g-1 h-1 (selectivity, ~100%) without the use of any sacrificial agents, which is more than ten times greater than that of single-component photocatalyst (Ni-TCPP) and greater than that of the most organic photocatalysts. The structure-function relationship was investigated by femtosecond transient absorption spectroscopy and density functional theory calculations. Our work provides new insight for designing efficient artificial photocatalysts, paving the way for the development of clean and renewable fuels through the conversion of CO2 using solar energy.

Mixed-Linker Strategy for the Construction of Sulfone-Containing D-A-A Covalent Organic Frameworks for Efficient Photocatalytic Hydrogen Peroxide Production.

The solar-driven photocatalytic production of hydrogen peroxide (H2O2) from water and oxygen using semiconductor catalysts offers a promising approach for converting solar energy into storable chemical energy. However, the efficiency of photocatalytic H2O2 production is often restricted by the low photo-generated charge separation, slow surface reactions and inadequate stability. Here, we developed a mixed-linker strategy to build a donor-acceptor-acceptor (D-A-A) type covalent organic framework (COF) photocatalyst, FS-OHOMe-COF. The FS-OHOMe-COF structure features extended π-π conjugation that improves charge mobility, while the introduction of sulfone units not only as active sites facilitates surface reactions with water but also bolsters stability through increased interlayer forces. The resulting FS-OHOMe-COF has a low exciton binding energy, long excited-state lifetime and high photo-stability that leads to high performance for photocatalytic H2O2 production (up to 1.0 mM h-1) with an H2O2 output of 19 mM after 72 hours of irradiation. Furthermore, the catalyst demonstrates high stability, which sustained activity over 192 hours of photocatalytic experiment.

Unprecedented Photocatalytic Hydrogen Peroxide Production via Covalent Triazine Frameworks Constructed from Fused Building Blocks.

Covalent organic frameworks (COFs) have garnered attention for their potential in photocatalytic hydrogen peroxide (H2O2) production. However, their photocatalytic efficiency is impeded by insufficient exciton dissociation and charge carrier transport. Constructing COFs with superior planarity is an effective way to enhance the π-conjugation degree and facilitate electron-hole separation. Nonetheless, the conventional linear linkers of COFs inevitably introduce torsional strain that disrupts coplanarity.Herein, we address this issue by introducing inherently coplanar triazine rings as linkers and fused building blocks as monomers to create covalent triazine frameworks (fused CTFs) with superior coplanarity. Both experimental and theoretical calculations confirm that CTFs constructed from fused building blocks significantly enhance the electron-hole separation efficiency and improve the photocatalytic performance, compared to the CTFs constructed with non-fused building blocks. The frontier molecular orbitals and electrostatic potentials (ESP) revealed that the ORR is preferentially facilitated by the triazine rings, with the WOR likely occurring at the thiophene-containing moiety. Remarkably, CTF-BTT achieved an exceptional H2O2 production rate of 74956 µmol g-1 h-1 when employing 10% benzyl alcohol (V/V) as a sacrificial agent in an O2-saturated atmosphere, surpassing existing photocatalysts by nearly an order of magnitude.

Covalent Organic Framework Nanohydrogels.

Nanohydrogelation of covalent organic frameworks (COFs) will undoubtedly open up new applications for them in water, such as aqueous catalysis and biomedicine. It is currently a great challenge to achieve water dispersion of COFs through either bottom-up construction strategies or top-down exfoliating technologies. Herein, poly(N-isopropylacrylamide) (PNIPAM)-postmodified COF nanohydrogels (COF-NHGs) are successfully designed and synthesized via in situ atom-transfer radical polymerization (ATRP) on a scaffold of COFs. During the polymer growth process, the bulk COFs are exfoliated into nanosheets with a lateral size of ∼500 nm and a thickness of ∼6.5 nm. Moreover, their size can be precisely controlled by the degree of polymerization of PNIPAMs. In aqueous solution, the obtained COF-NHGs are assembled into nanohydrogels retaining intra-plane crystallinity and exhibit a temperature-sensitive sol-gel phase transition. With excellent solubility in organic solvents, the COF-NHGs' intrinsic physical properties in the solution state can be characterized through their solution nuclear magnetic resonance and ultraviolet absorption spectra. These results put forward new opportunities for regulating the solution processability of COFs and building an intelligent, stimuli-response platform of COF-polymer composite nanohydrogels for device applications.

Arabidopsis NPF2.13 functions as a critical transporter of bacterial natural compound tunicamycin in plant-microbe interaction.

Metabolites including antibiotics, enzymes, and volatiles produced by plant-associated bacteria are key factors in plant-microbiota interaction that regulates various plant biological processes. There should be crucial mediators responsible for their entry into host plants. However, less is known about the identities of these plant transporters. We report that the Arabidopsis Nitrate Transporter1 (NRT1)/NPF protein NPF2.13 functions in plant uptake of tunicamycin (TM), a natural antibiotic produced by several Streptomyces spp., which inhibits protein N-glycosylation. Loss of NPF2.13 function resulted in enhanced TM tolerance, whereas NPF2.13 overexpression led to TM hypersensitivity. Transport assays confirmed that NPF2.13 is a H+ /TM symporter and the transport is not affected by other substrates like nitrate. NPF2.13 exclusively showed TM transport activity among tested NPFs. Tunicamycin uptake from TM-producing Streptomyces upregulated the expression of nitrate-related genes including NPF2.13. Moreover, nitrate allocation to younger leaves was promoted by TM in host plants. Tunicamycin could also benefit plant defense against the pathogen. Notably, the TM effects were significantly repressed in npf2.13 mutant. Overall, this study identifies NPF2.13 protein as an important TM transporter in plant-microbe interaction and provides insights into multiple facets of NPF proteins in modulating plant nutrition and defense by transporting exterior bacterial metabolites.

Covalent Triazine Frameworks (CTFs): Synthesis, Crystallization, and Photocatalytic Water Splitting.

Covalent Triazine Frameworks (CTFs) have received great attention from academia owing to their unique structure characteristics such as nitrogen-rich structure, chemical stability, fully conjugated skeleton and high surface area; all these unique properties make CTFs attractive for widespread applications, especially for photocatalytic applications. In this review, we aim to provide recent advances in the CTFs preparation, and mainly focus on their photocatalytic applications. This review provides a comprehensive and systematic overview of the CTFs' synthetic methods, crystallinity lifting strategies, and their applications for photocatalytic water splitting. Firstly, a brief background including the photocatalytic water splitting and crystallinity are provided. Then, synthetic methods related to CTFs and the strategies for enhancing the crystallinity are summarized and compared. After that, the general photocatalytic mechanism and the strategies to improve the photocatalytic performance of CTFs are discussed. Finally, the perspectives and challenges of fabricating high crystalline CTFs and designing CTFs with excellent photocatalytic performance are discussed, inspiring the development of CTF materials in photocatalytic applications.