AKT2 deficiency alleviates doxorubicin-induced cardiac injury via alleviating oxidative stress in cardiomyocytes.

Doxorubicin (DOX), a widely used chemotherapy agent in cancer treatment, encounters limitations in clinical efficacy due to associated cardiotoxicity. This study aims to explore the role of AKT serine/threonine kinase 2 (AKT2) in mitigating DOX-induced oxidative stress within the heart through both intracellular and extracellular signaling pathways. Utilizing Akt2 knockout (KO) and Nrf2 KO murine models, alongside neonatal rat cardiomyocytes (NRCMs), we systematically investigate the impact of AKT2 deficiency on DOX-induced cardiac injury. Our findings reveal that DOX administration induces significant oxidative stress, a primary contributor to cardiac injury. Importantly, Akt2 deficiency exhibits a protective effect by alleviating DOX-induced oxidative stress. Mechanistically, Akt2 deficiency facilitates nuclear translocation of NRF2, thereby suppressing intracellular oxidative stress by promoting the expression of antioxidant genes. Furthermore, We also observed that AKT2 inhibition facilitates superoxide dismutase 2 (SOD2) expression both inside macrophages and SOD2 secretion to the extracellular matrix, which is involved in lowering oxidative stress in cardiomyocytes upon DOX stimulation. The present study underscores the important role of AKT2 in mitigating DOX-induced oxidative stress through both intracellular and extracellular signaling pathways. Additionally, our findings propose promising therapeutic strategies for addressing DOX-induced cardiomyopathy in clinic.

The novel norcantharidin derivative DCZ5417 suppresses multiple myeloma progression by targeting the TRIP13-MAPK-YWHAE signaling pathway.

BACKGROUND: Multiple myeloma (MM), an incurable disease owing to drug resistance, requires safe and effective therapies. Norcantharidin (NCTD), an active ingredient in traditional Chinese medicines, possesses activity against different cancers. However, its toxicity and narrow treatment window limit its clinical application. In this study, we synthesized a series of derivatives of NCTD to address this. Among these compounds, DCZ5417 demonstrated the greatest anti-MM effect and fewest side effects. Its anti-myeloma effects and  the mechanism were further tested. METHODS: Molecular docking, pull-down, surface plasmon resonance-binding, cellular thermal shift, and ATPase assays were used to study the targets of DCZ5417. Bioinformatic, genetic, and pharmacological approaches were used to elucidate the mechanisms associated with DCZ5417 activity. RESULTS: We confirmed a highly potent interaction between DCZ5417 and TRIP13. DCZ5417 inhibited the ATPase activity of TRIP13, and its anti-MM activity was found to depend on TRIP13. A mechanistic study verified that DCZ5417 suppressed cell proliferation by targeting TRIP13, disturbing the TRIP13/YWHAE complex and inhibiting the ERK/MAPK signaling axis. DCZ5417 also showed a combined lethal effect with traditional anti-MM drugs. Furthermore, the tumor growth-inhibitory effect of DCZ5417 was demonstrated using in vivo tumor xenograft models. CONCLUSIONS: DCZ5417 suppresses MM progression in vitro, in vivo, and in primary cells from drug-resistant patients, affecting cell proliferation by targeting TRIP13, destroying the TRIP13/YWHAE complex, and inhibiting ERK/MAPK signaling. These results imply a new and effective therapeutic strategy for MM treatment.

Auto-inhibition and activation of a short Argonaute-associated TIR-APAZ defense system.

Short prokaryotic Ago accounts for most prokaryotic Argonaute proteins (pAgos) and is involved in defending bacteria against invading nucleic acids. Short pAgo associated with TIR-APAZ (SPARTA) has been shown to oligomerize and deplete NAD+ upon guide-mediated target DNA recognition. However, the molecular basis of SPARTA inhibition and activation remains unknown. In this study, we determined the cryogenic electron microscopy structures of Crenotalea thermophila SPARTA in its inhibited, transient and activated states. The SPARTA monomer is auto-inhibited by its acidic tail, which occupies the guide-target binding channel. Guide-mediated target binding expels this acidic tail and triggers substantial conformational changes to expose the Ago-Ago dimerization interface. As a result, SPARTA assembles into an active tetramer, where the four TIR domains are rearranged and packed to form NADase active sites. Together with biochemical evidence, our results provide a panoramic vision explaining SPARTA auto-inhibition and activation and expand understanding of pAgo-mediated bacterial defense systems.

A neonatal case report of branchiooculofacial syndrome caused by a novel mutation in the TFAP2A gene and literature review.

RATIONALE: Branchiooculofacial syndrome (BOFS) is a rare autosomal dominant disorder with a diverse clinical phenotype. To summarise the clinical characteristics and genetic variations of neonatal-onset BOFS through a case study and literature review. PATIENT CONCERNS: A preterm neonate with a very low birth weight, born at a gestational age of 29+3 weeks, exhibited cosmetic abnormalities at a postmenstrual age of 34+6 weeks, including microcleft lip, high arched palate, curved upper lip, low ear position, and ocular hypertelorism. Hence, a genetic test on peripheral blood was carried out. DIAGNOSES: The genetic testing showed a heterozygous variant of c.724G > A (p.Glu242Lys) in the exon 4 region of the TFAP2A (transcription factor AP-2-α) gene in the short arm of chromosome 6. BOFS was confirmed based on clinical appearance and the genetic result. INTERVENTIONS: The patient underwent solely cleft lip repair at the age of 6 months with no further intervention. OUTCOMES: The infant shows normal growth and development at 1 year of age and subsequent follow-up. LESSONS: The characteristic facial features, branchial skin defects, and ocular anomalies are the main clinical manifestations of BOFS with neonatal onset, but the diverse clinical phenotype and variable genetic variants pose certain challenges for clinical diagnosis.

Mammalian trans-editing factor ProX is able to deacylate tRNAThr mischarged with alanine.

The precise coupling of tRNAs with their cognate amino acids, known as tRNA aminoacylation, is a stringently regulated process that governs translation fidelity. To ensure fidelity, organisms deploy multiple layers of editing mechanisms to correct mischarged tRNAs. Prior investigations have unveiled the propensity of eukaryotic AlaRS to erroneously attach alanine onto tRNACys and tRNAThr featuring the G4:U69 base pair. In light of this, and given ProXp-ala's capacity in deacylating Ala-tRNAPro, we embarked on exploring whether this trans-editing factor could extend its corrective function to encompass these mischarged tRNAs. Our in vitro deacylation assays demonstrate that murine ProXp-ala (mProXp-ala) is able to efficiently hydrolyze Ala-tRNAThr, while Ala-tRNACys remains unaffected. Subsequently, we determined the first structure of eukaryotic ProXp-ala, revealing a dynamic helix α2 involved in substrate binding. By integrating molecular dynamics simulations and biochemical assays, we pinpointed the pivotal interactions between mProXp-ala and Ala-tRNA, wherein the basic regions of mProXp-ala as well as the C3-G70 plays essential role in recognition. These observations collectively provide a cogent rationale for mProXp-ala's deacylation proficiency against Ala-tRNAThr. Our findings offer valuable insights into the translation quality control within higher eukaryotic organisms, where the fidelity of translation is safeguarded by the multi-functionality of extensively documented proteins.

Design of a chimeric glycosyltransferase OleD for the site-specific O-monoglycosylation of 3-hydroxypyridine in nosiheptide.

To identify the potential role of the 3-hydroxyl group of the pyridine ring in nosiheptide (NOS) for its antibacterial activity against Gram-positive pathogens, enzymatic glycosylation was utilized to regio-selectively create a monoglycosyl NOS derivative, NOS-G. For this purpose, we selected OleD, a UDP glycosyltransferase from Streptomyces antibioticus that has a low productivity for NOS-G. Activity of the enzyme was increased by swapping domains derived from OleI, both single and in combination. Activity enhancement was best in mutant OleD-10 that contained four OleI domains. This chimer was engineered by site-directed mutagenesis (single and in combination) to increase its activity further, whereby variants were screened using a newly-established colorimetric assay. OleD-10 with I117F and T118G substitutions (FG) had an increased NOS-G productivity of 56%, approximately 70 times higher than that of wild-type OleD. The reason for improved activity of FG towards NOS was structurally attributed to a closer distance (<3 Å) between NOS/sugar donor and the catalytic amino acid H25. The engineered enzyme allowed sufficient activity to demonstrate that the produced NOS-G had enhanced stability and aqueous solubility compared to NOS. Using a murine MRSA infection model, it was established that NOS-G resulted in partial protection within 20 h of administration and delayed the death of infected mice. We conclude that 3-hydroxypyridine is a promising site for structural modification of NOS, which may pave the way for producing nosiheptide derivatives as a potential antibiotic for application in clinical treatment.

Metabolomics Reveals Distinctive Metabolic Profiles and Marker Compounds of Camellia (Camellia sinensis L.) Bee Pollen.

Camellia bee pollen (CBP) is a major kind of bee product which is collected by honeybees from tea tree (Camellia sinensis L.) flowers and agglutinated into pellets via oral secretion. Due to its special healthcare value, the authenticity of its botanical origin is of great interest. This study aimed at distinguishing CBP from other bee pollen, including rose, apricot, lotus, rape, and wuweizi bee pollen, based on a non-targeted metabolomics approach using ultra-high performance liquid chromatography-mass spectrometry. Among the bee pollen groups, 54 differential compounds were identified, including flavonol glycosides and flavone glycosides, catechins, amino acids, and organic acids. A clear separation between CBP and all other samples was observed in the score plots of the principal component analysis, indicating distinctive metabolic profiles of CBP. Notably, L-theanine (864.83-2204.26 mg/kg) and epicatechin gallate (94.08-401.82 mg/kg) were identified exclusively in all CBP and were proposed as marker compounds of CBP. Our study unravels the distinctive metabolic profiles of CBP and provides specific and quantified metabolite indicators for the assessment of authentic CBP.

Mechanistic insights into transposon cleavage and integration by TnsB of ShCAST system.

The type V-K CRISPR-associated transposons (CASTs) allow RNA-guided DNA integration and have great potential as a programmable site-specific gene insertion tool. Although all core components have been independently characterized structurally, the mechanism of how the transposase TnsB associates with AAA+ ATPase TnsC and catalyzes donor DNA cleavage and integration remains ambiguous. In this study, we demonstrate that TniQ-dCas9 fusion can direct site-specific transposition by TnsB/TnsC in ShCAST. TnsB is a 3'-5' exonuclease that specifically cleaves donor DNA at the end of the terminal repeats and integrates the left end prior to the right end. The nucleotide preference and the cleavage site of TnsB are markedly different from those of the well-documented MuA. We also find that TnsB/TnsC association is enhanced in a half-integration state. Overall, our results provide valuable insights into the mechanism and application expansion of CRISPR-mediated site-specific transposition by TnsB/TnsC.

Regulation of Intracellular Reactive Oxygen Species Levels after the Development of Phallus rubrovolvatus Rot Disease Due to Trichoderma koningii Mycoparasitism.

Phallus rubrovolvatus is a unique mushroom used for medicinal and dietary purposes in China. In recent years, however, the rot disease of P. rubrovolvatus has seriously affected its yield and quality, becoming an economically important threat. In this study, samples of symptomatic tissues were collected, isolated, and identified from five major P. rubrovolvatus production regions in Guizhou Province, China. Based on combined analyses of phylogenies (ITS and EF1-α), morphological characteristics and Koch's postulates, Trichoderma koningiopsis and Trichoderma koningii were identified as the pathogenic fungal species. Among these, T. koningii exhibited stronger pathogenicity than the other strains; thus, T. koningii was used as the test strain in the follow-up experiments. Upon co-culturing T. koningii with P. rubrovolvatus, the hyphae of the two species were intertwined, and the color of the P. rubrovolvatus hyphae changed from white to red. Moreover, T. koningii hyphae were wrapped around P. rubrovolvatus hyphae, leading to their shortening and convolution and ultimately inhibiting their growth due to wrinkling; T. koningii penetrated the entire basidiocarp tissue of P. rubrovolvatus, causing serious damage to the host basidiocarp cells. Further analyses revealed that T. koningii infection resulted in the swelling of basidiocarps and significantly enhanced the activity of defense-related enzymes, such as malondialdehyde, manganese peroxidase, and polyphenol oxidase. These findings offer theoretical support for further research on the infection mechanisms of pathogenic fungi and the prevention of diseases caused by them.

Structure and function characterization of the α-L-arabinofuranosidase from the white-rot fungus Trametes hirsuta.

α-L-Arabinofuranosidases (Abfs) play a crucial role in the degradation of hemicelluloses, especially arabinoxylans (AX). Most of the available characterized Abfs are from bacteria, while fungi, as natural decomposers, contain Abfs with little attention given. An arabinofuranosidase (ThAbf1), belonging to the glycoside hydrolase 51 (GH51) family, from the genome of the white-rot fungus Trametes hirsuta, was recombinantly expressed, characterized, and functionally determined. The general biochemical properties showed that the optimal conditions for ThAbf1 were pH 6.0 and 50°C. In substrate kinetics assays, ThAbf1 preferred small fragment arabinoxylo-oligosaccharides (AXOS) and could surprisingly hydrolyze di-substituted 23,33-di-L-arabinofuranosyl-xylotriose (A2,3XX). It also synergized with commercial xylanase (XYL) and increased the saccharification efficiency of arabinoxylan. The crystal structure of ThAbf1 indicated the presence of an adjacent cavity next to the catalytic pocket which led to the ability of ThAbf1 to degrade di-substituted AXOS. The narrow binding pocket prevents ThAbf1 from binding larger substrates. These findings have strengthened our understanding of the catalytic mechanism of GH51 family Abfs and provided a theoretical foundation for the development of more efficient and versatile Abfs to accelerate the degradation and biotransformation of hemicellulose in biomass. KEY POINTS: • ThAbf1 from Trametes hirsuta degraded di-substituted arabinoxylo-oligosaccharide. • ThAbf1 performed detailed biochemical characterization and kinetics. • ThAbf1 structure has been obtained to illustrate the substrate specificity.

Highly stable Ru-complex-based metal-covalent organic frameworks as novel type of electrochemiluminescence emitters for ultrasensitive biosensing.

Developing novel types of high-performance electrochemiluminescence (ECL) emitters is of great significance for constructing ultrasensitive ECL sensors. Herein, a highly stable metal-covalent organic framework (MCOF), termed Ru-MCOF, has been devised and synthesized by employing a classic ECL luminophore, tris(4,4'-dicarboxylicacid-2,2'-bipyridyl)ruthenium(II) (Ru(dcbpy)32+), as building unit and applied as a novel ECL probe to construct an ultrasensitive ECL sensor for the first time. Impressively, the topologically ordered and porous architectures of the Ru-MCOF not only allow Ru(bpy)32+ units to precisely locate and homogeneously distribute in the skeleton via strong covalent bonds but also facilitate the transport of co-reactants and electrons/ions in channels to promote the electrochemical activation of both external and internal Ru(bpy)32+ units. All these features endow the Ru-MCOF with excellent ECL emission, high ECL efficiency, and outstanding chemical stability. As expected, the constructed ECL biosensor based on the Ru-MCOF as a high-efficiency ECL probe accomplishes the ultrasensitive detection of microRNA-155. Overall, the synthesized Ru-MCOF not only enriches the MCOF family but also displays excellent ECL performance and thus expands the application of MCOFs in bioassays. Considering the structural diversity and tailorability of MCOFs, this work opens a new horizon to design and synthesize high-performance ECL emitters, therefore paving a new way to develop highly stable and ultrasensitive ECL sensors and motivating further research on MCOFs.

Discovery of quinazolin-4-one-based non-covalent inhibitors targeting the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 Mpro).

The COVID-19 pandemic caused by SARS-CoV-2 continues to pose a great threat to public health while various vaccines are available worldwide. Main protease (Mpro) has been validated as an effective anti-COVID-19 drug target. Using medicinal chemistry and rational drug design strategies, we identified a quinazolin-4-one series of nonpeptidic, noncovalent SARS-CoV-2 Mpro inhibitors based on baicalein, 5,6,7-trihydroxy-2-phenyl-4H-chromen-4-one. In particular, compound C7 exhibits superior inhibitory activity against SARS-CoV-2 Mpro relative to baicalein (IC50 = 0.085 ± 0.006 and 0.966 ± 0.065 µM, respectively), as well as improved physicochemical and drug metabolism and pharmacokinetics (DMPK) properties. In addition, C7 inhibits viral replication in SARS-CoV-2-infected Vero E6 cells more effectively than baicalein (EC50 = 1.10 ± 0.12 and 5.15 ± 1.64 µM, respectively) with low cytotoxicity (CC50 ＞ 50 µM). An X-ray co-crystal structure reveals a non-covalent mechanism of action, and a noncanonical binding mode not observed by baicalein. These results suggest that C7 represents a promising lead for development of more effective SARS-CoV-2 Mpro inhibitors and anti-COVID-19 drugs.

Target and non-target analysis of organochlorine pesticides and their transformation products in an agrochemical-contaminated area.

Organochlorine pesticides show biological toxicity and their degradation typically takes many years. Previous studies of agrochemical-contaminated areas have mainly focused on limited target compounds, and emerging pollutants in soil have been overlooked. In this study, we collected soil samples from an abandoned agrochemical-contaminated area. Target analysis and non-target suspect screening by gas chromatography coupled with time-of-flight mass spectrometry were combined for qualitative and quantitative analysis of organochlorine pollutants. Target analysis showed that dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), and dichlorodiphenyldichloroethane (DDD) were the main pollutants. With concentrations between 3.96 × 106 and 1.38 × 107 ng/g, these compounds posed significant health risks at the contaminated site. Non-target suspect screening identified 126 organochlorine compounds, most of which were chlorinated hydrocarbons and 90% of the compounds contained a benzene ring structure. The possible transformation pathways of DDT were inferred from proven pathways and the compounds identified by non-target suspect screening that had similar structures to DDT. This study will be useful for studies of the degradation mechanism of DDT. Semi-quantitative and hierarchical cluster analysis of compounds in soil showed that the distribution of contaminants in soil was influenced by the types of pollution sources and distance to them. Twenty-two contaminants were found in the soil at relatively high concentrations. The toxicities of 17 of these compounds are currently not known. These results improve our understanding of the environmental behavior of organochlorine contaminants in soil and are useful for further risk assessments of agrochemical-contaminated areas.

A new monocyclic monoterpene derivative from volva of Phallus dongsun.

A new monoterpene derivative namely dongsunol A (1) and sixteen known compounds (2-17) were isolated from the volva of Phallus dongsun. All compounds were isolated from this fungus for the first time. Their structures and absolute configurations were determined by nuclear magnetic resonance (NMR), HRESIMS spectral data, and electronic circular dichroism (ECD). The new monoterpene derivative (1) exhibited antibacterial activity with a MIC of 200 µg/mL. Other compounds have inhibitory effects on Staphylococcus aureus and Pseudomonas aeruginosa, while have displayed moderate NO inhibitory activity and antineoplastic activity on SMMC-7721 and SW480 in vitro.

ROS Scavenging and inflammation-directed polydopamine nanoparticles regulate gut immunity and flora therapy in inflammatory bowel disease.

Dysfunction of the intestinal mucosal immune system and dysbiosis of the intestinal microflora can induce inflammatory bowel disease. However, drug-mediated clinical treatment remains a challenge due to its poor therapeutic efficacy and severe side effects. Herein, a ROS scavenging and inflammation-directed nanomedicine is designed and fabricated by coupling polydopamine nanoparticles with mCRAMP, an antimicrobial peptide, while wrapping macrophage membrane in the outer layer. The designed nanomedicine reduced the secretion of pro-inflammatory cytokines and elevate the expression of anti-inflammatory cytokine in vivo and in vitro inflammation models, demonstrating its significant ability of improving inflammatory responses. Importantly, the macrophage membrane encapsulated nanoparticles exhibit the obviously enhanced targeting performance in local inflamed tissues. Furthermore, the 16S rRNA sequencing of fecal microorganisms showed that probiotics increased and pathogenic bacteria were inhibited after oral delivery the nanomedicine, indicating that the designed nano platform played a significant role in optimizing intestinal microbiome. Taken together, the designed nanomedicine are not only easy to prepare and exhibit high biocompatibility, but also show the inflammatory targeting property, anti-inflammatory function and positive regulation of intestinal flora, thus providing a new idea for the intervention and treatment of colitis. STATEMENT OF SIGNIFICANCE: Inflammatory bowel disease (IBD), a chronic and intractable disease, may lead to colon cancer in severe cases without effective treatment. However, clinical drugs are largely ineffective owing to insufficient therapeutic efficacies and side effects. Herein, we constructed a biomimetic polydopamine nanoparticle for oral administration to treat the IBD by modulating mucosal immune homeostasis and optimizing intestinal microorganisms. In vitro and in vivo experiments showed that the designed nanomedicine not only exhibits the anti-inflammatory function and inflammatory targeting property but also positively regulate the gut microflora. Taken together, the designed nanomedicine combined immunoregulation and intestinal microecology modulation to significantly enhance the therapeutic effect on colitis in mice, thus providing a new approach for the clinical treatment of colitis.

Ruthenium(II) complex-grafted conductive metal-organic frameworks with conductivity- and confinement-enhanced electrochemiluminescence for ultrasensitive biosensing application.

Improving the electrochemiluminescence (ECL) performance of luminophores is an ongoing research hotspot in the ECL realm. Herein, a high-performance metal-organic framework (MOF)-based ECL material (Ru@Ni3(HITP)2, HITP = 2,3,6,7,10,11-hexaiminotriphenylene) with conductivity- and confinement-enhanced ECL was successfully constructed by using conductive MOF Ni3(HITP)2 as the carrier to graft Ru(bpydc)34- (H2bpydc = 2,2'-bipyridine-4,4'-dicarboxylic acid) into the channels of Ni3(HITP)2. Compared to Ru@Cu3(HITP)2 and Ru@Co3(HITP)2 with relatively low conductivity, the ECL intensity of Ru@Ni3(HITP)2 was prominently increased about 6.76 times and 18.8 times, respectively, which demonstrated that the increase in conductivity induced the ECL enhancement of the MOF-based ECL materials. What's more, the hydrophobic and porous Ni3(HITP)2 can not only effectively enrich the lipophilic tripropylamine (TPrA) coreactants in its channels to enhance the electrochemical oxidation efficiency of TPrA, but also provide a conductive reaction micro-environment to boost the ECL reaction between Ru(bpydc)33- intermediates and TPrA• in confined spaces, thus realizing a remarkable confinement-enhanced ECL. Considering the excellent ECL performance of Ru@Ni3(HITP)2, an ultrasensitive ECL biosensor was prepared based on the Ru@Ni3(HITP)2 ECL indicator combining an exonuclease I-aided target cycling amplification strategy for thrombin determination. The constructed ECL biosensor showcased a wide linear range from 1 fM to 1 nM with a low detection limit of 0.62 fM. Overall, the conductivity- and confinement-enhanced ECL based on Ru@Ni3(HITP)2 provided effective and feasible strategies to enhance ECL performance, which paved a promising avenue for exploring high-efficient MOF-based ECL materials and thus broadened the application scope of conductive MOFs.

Pyrene-Based Hydrogen-Bonded Organic Frameworks as New Emitters with Porosity- and Aggregation-Induced Enhanced Electrochemiluminescence for Ultrasensitive MicroRNA Assay.

Exploring new electrochemiluminescence (ECL) luminophores with strong ECL emission is highly desirable for developing ultrasensitive ECL sensors. Herein, a pyrene-based hydrogen-bonded organic framework (Py-HOF) featuring prominent ECL performance was prepared by utilizing 1,3,6,8-tetrakis(p-benzoic acid) pyrene (H4TBAPy) with an aggregation-induced enhanced emission (AIEE) property as a building block, exhibiting a stronger ECL emission than those of H4TBAPy monomers, H4TBAPy aggregates, the low-porosity Py-HOF-210 °C and Py-HOF-180 °C. We have coined the term "the porosity- and aggregation-induced enhanced ECL (PAIE-ECL)" for this intriguing phenomenon. The Py-HOF displayed superb and stable ECL intensity, not only because the luminophore H4TBAPy was assembled into the Py-HOF via four pairs of O-H···O hydrogen bonds, which constrained the intramolecular movements to reduce nonradiative transition, but also because the H4TBAPy in Py-HOF was stacked in a slipped face-to-face mode to form J-aggregates that benefited the ECL enhancement. Furthermore, the high porosity of Py-HOF allowed the enrichment of coreactants and facilitated the migration of ions, electrons, and coreactants, which made it possible for the inner and outer H4TBAPy to be electrochemically excited. Considering the remarkable ECL performance, Py-HOF was first employed as an ECL probe combined with a 3D DNA nanomachine amplification strategy to assemble a hypersensitive "on-off" ECL sensor for the microRNA-141 assay, presenting a satisfactory linear range (100 aM to 1 nM) with a detection limit of 14.4 aM. The PAIE-ECL manifested by Py-HOF provided a bright avenue for the design and synthesis of outstanding HOF-based ECL materials and offered new opportunities for the development of ECL biosensors with excellent sensitivity.

Feasibility and basic acoustic characteristics of intelligent long-term bowel sound analysis in term neonates.

Objective: Bowel dysfunction continues to be a serious issue in neonates. Traditional auscultation of bowel sounds as a diagnostic tool in neonatal gastrointestinal problems is limited by skill and inability to document and reassess. Consequently, in order to objectively and noninvasively examine the viability of continuous assessment of bowel sounds, we utilized an acoustic recording and analysis system to capture bowel sounds and extract acoustic features in term neonates. Methods: From May 1, 2020 to September 30, 2020, 82 neonates who were hospitalized because of hyperbilirubinemia were included. For 20 h, a convolutional neural network-based acoustic recorder that offers real-time, wireless, continuous auscultation was employed to track the bowel sounds of these neonates. Results: (1) Usable data on five acoustic parameters of bowel sound was recorded for 68 neonates, and the median values were as follows: The rate was 25.80 times/min [interquartile range (IQR): 15.63-36.20]; the duration was 8.00 s/min (IQR: 4.2-13.20); the amplitude was 0.46 (IQR: 0.27-0.68); the frequency was 944.05 Hz (IQR: 848.78-1,034.90); and the interval time was 2.12 s (IQR: 1.3-3.5). (2) In comparison to the parameters of the bowel sounds recorded from the right lower abdomen in 68 infants, the acoustic parameters of the 10 out of 68 infants from chest controls and blank controls were considerably different. (3) The 50%-75% breast milk intake group had the highest rate, the longest duration, and the highest amplitude of bowel sounds, while the >75% breast milk intake group had the highest frequency of bowel sounds. (4) Compared with neonates without hyperbilirubinemia, there was no significant difference in the five parameters of bowel sounds in hyperbilirubinemia infants; nor was there a significant effect of phototherapy and non-phototherapy status on the parameters of bowel sounds during bowel sound monitoring in hyperbilirubinemia patients. (5) A mild transient skin rash appeared on the skin of three infants. No other adverse events occurred. Conclusion: The acoustic recording and analysis system appears useful for monitoring bowel sounds using a continuous, invasive, and real-time approach. Neonatal bowel sounds are affected by various feeding types rather than hyperbilirubinemia and phototherapy. Potential influencing factors and the significance of their application in neonatal intestinal-related disorders require further research.

Metabarcoding and Metabolome Analyses Reveal Mechanisms of Leymus chinensis Growth Promotion by Fairy Ring of Leucocalocybe mongolica.

Fairy rings are a unique ecological phenomenon caused by the growth of the fungal mycelium in the soil. Fairy rings formed by Leucocalocybe mongolica (LM) are generally distributed in the Mongolian Plateau, where they promote plant growth without fertilization and alleviate fertilizer use. We previously investigated the soil factors regulating growth promotion in a fairy ring ecosystem; however, the aspects of the plant (Leymus chinensis, LC) that promote growth have not been explored. Therefore, the present study investigated the endophyte diversity and metabolome of LC in an LM fairy ring ecosystem. We analyzed the leaf and root samples of LC from the DARK (FR) and OUT (CK) zones. The fairy rings significantly improved the fungal diversity of roots and leaves and the bacterial diversity of leaves in the FR zone. Ralstonia was the dominant bacteria detected in the LC leaves. In addition, Marasmius, another fairy ring fungal genus, was also detected with a high abundance in the roots of the FR zone. Furthermore, widely targeted metabolome analysis combined with KEGG annotation identified 1011 novel metabolites from the leaves and roots of LC and seven pathways significantly regulated by the fairy ring in the FR zone. The fairy ring ecosystem significantly downregulated the flavonoid metabolism in the leaves and roots of LC. The correlation analysis found Ralstonia is a potential regulatory factor of flavonoid biosynthesis in LC. In addition, salicylic acid and jasmonic acid were found upregulated in the leaves, probably related to Marasmius enrichment. Thus, the study details plant factors associated with enhanced growth in an LM fairy ring ecosystem. These findings lay a theoretical foundation for developing the fairy ring ecosystem in an agricultural system.

Soil Chemical Properties, Metabolome, and Metabarcoding Give the New Insights into the Soil Transforming Process of Fairy Ring Fungi Leucocalocybe mongolica.

A unique ecological landscape distributed in the Mongolian Plateau, called fairy rings, caused by the growth of the fungus Leucocalocybe mongolica (LM) in the soil could promote plant growth without fertilization. Therefore, this landscape can alleviate fertilizer use and has excellent value for agricultural production. The previous studies only investigated several parameters of the fairy rings, such as soil microbial diversity and some soil chemical properties, thus conclusions based on the studies on fairy rings lack comprehension. Therefore, the present study systematically investigated the chemical properties, metabolome, and metabarcoding of LM-transformed soil. We analyzed fairy ring soils from DARK (FR) and OUT (CK) zone correlated growth promotion with ten soil chemical properties, including N, nitrate-N, inorganic-P, cellulose, available boron, available sulfur, Fe, Mn, Zn, and Cu, which were identified as important markers to screen fairy ring landscapes. Metabolomics showed that the accumulation of 17 carbohydrate-dominated metabolites was closely associated with plant growth promotion. Finally, metabarcoding detected fungi as the main components affecting soil conversion. Among the various fungi at the family level, Lasiosphaeriaceae, unidentified_Auriculariales_sp, and Herpotrichiellaceae were markers to screen fairy ring. Our study is novel and systematically reveals the fairy ring soil ecology and lists the key factors promoting plant growth. These findings lay a theoretical foundation for developing the fairy ring landscape in an agricultural system.