Effect of chitosan/dioleyl phosphatidyl ethanolamine - Baicalein nanohydrogel in the treatment of rat with periodontitis.

Objective: this work aimed to investigate the effectiveness of chitosan (CS)/dioleyl phosphatidyl ethanolamine (DOPE) - baicalein (CS/DOPE-BAE) nanohydrogel as a novel drug delivery system for the treatment of periodontitis in rats. Materials and methods: the CS/DOPE-BAE nanohydrogel was synthesized and characterized for its morphology, particle size (PS), drug loading, and release properties. A rat periodontitis model was established, and the rats were randomly assigned to four groups, receiving treatment of normal saline, CS/DOPE blank nanohydrogel, baicalein solution, and CS/DOPE-BAE nanohydrogel through local injection, respectively. Clinical symptoms, periodontal tissue morphology, and the levels of interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α), and IL-10 in the periodontal tissue were observed and compared. Results: the CS/DOPE-BAE nanohydrogel exhibited a spherical shape with a PS of approximately 200 nm and a drug loading of 8.6 %. It demonstrated excellent sustained-release properties. The group treated with CS/DOPE-BAE nanohydrogel showed significant improvement in clinical symptoms, such as reduced gingival redness and bleeding in rats, decreased inflammatory cell infiltration, and weakened fibroblast proliferation in the periodontal tissue. Additionally, IL-1ß and TNF-α levels were downregulated, while IL-10 level was elevated. Conclusion: the CS/DOPE-BAE nanohydrogel was an effective baicalein delivery system that can inhibit the progression of periodontitis, improve the inflammatory response in periodontal tissue, and deliver promising therapeutic effects.

A multifunctional flavoprotein monooxygenase HspB for hydroxylation and C-C cleavage of 6-hydroxy-3-succinoyl-pyridine.

Flavoprotein monooxygenases catalyze reactions, including hydroxylation and epoxidation, involved in the catabolism, detoxification, and biosynthesis of natural substrates and industrial contaminants. Among them, the 6-hydroxy-3-succinoyl-pyridine (HSP) monooxygenase (HspB) from Pseudomonas putida S16 facilitates the hydroxylation and C-C bond cleavage of the pyridine ring in nicotine. However, the mechanism for biodegradation remains elusive. Here, we refined the crystal structure of HspB and elucidated the detailed mechanism behind the oxidative hydroxylation and C-C cleavage processes. Leveraging structural information about domains for binding the cofactor flavin adenine dinucleotide (FAD) and HSP substrate, we used molecular dynamics simulations and quantum/molecular mechanics calculations to demonstrate that the transfer of an oxygen atom from the reactive FAD peroxide species (C4a-hydroperoxyflavin) to the C3 atom in the HSP substrate constitutes a rate-limiting step, with a calculated reaction barrier of about 20 kcal/mol. Subsequently, the hydrogen atom was rebounded to the FAD cofactor, forming C4a-hydroxyflavin. The residue Cys218 then catalyzed the subsequent hydrolytic process of C-C cleavage. Our findings contribute to a deeper understanding of the versatile functions of flavoproteins in the natural transformation of pyridine and HspB in nicotine degradation.IMPORTANCEPseudomonas putida S16 plays a pivotal role in degrading nicotine, a toxic pyridine derivative that poses significant environmental challenges. This study highlights a key enzyme, HspB (6-hydroxy-3-succinoyl-pyridine monooxygenase), in breaking down nicotine through the pyrrolidine pathway. Utilizing dioxygen and a flavin adenine dinucleotide cofactor, HspB hydroxylates and cleaves the substrate's side chain. Structural analysis of the refined HspB crystal structure, combined with state-of-the-art computations, reveals its distinctive mechanism. The crucial function of Cys218 was never discovered in its homologous enzymes. Our findings not only deepen our understanding of bacterial nicotine degradation but also open avenues for applications in both environmental cleanup and pharmaceutical development.

Molecular characterization of a novel narnavirus infecting the phytopathogenic fungus Botryosphaeria dothidea.

Here, a novel mycovirus, Botryosphaeria dothidea narnavirus 5 (BdNV5), was discovered in the plant-pathogenic fungus Botryosphaeria dothidea strain ZM210167-1. The BdNV5 genome sequence is 2,397 nucleotides (nt) in length and contains a putative open reading frame (ORF) encoding an RNA-dependent RNA polymerase (RdRp) with a molecular mass of 72.77 kDa. A BLASTp search using the RdRp amino acid (aa) sequence showed that it was most similar to the RdRp of Botryosphaeria dothidea narnavirus 4 (42.35%). In a phylogenetic tree based on RdRp aa sequences, BdNV5 clustered with members of the family Narnaviridae. BdNV5 is thus a novel member of the family Narnaviridae infecting the phytopathogenic fungus B. dothidea.

An Overview of Polymeric Nanoplatforms to Deliver Veterinary Antimicrobials.

There is an urgent need to find new solutions for the global dilemma of increasing antibiotic resistance in humans and animals. Modifying the performance of existing antibiotics using the nanocarrier drug delivery system (DDS) is a good option considering economic costs, labor costs, and time investment compared to the development of new antibiotics. Numerous studies on nanomedicine carriers that can be used for humans are available in the literature, but relatively few studies have been reported specifically for veterinary pharmaceutical products. Polymer-based nano-DDS are becoming a research hotspot in the pharmaceutical industry owing to their advantages, such as stability and modifiability. This review presents current research progress on polymer-based nanodelivery systems for veterinary antimicrobial drugs, focusing on the role of polymeric materials in enhancing drug performance. The use of polymer-based nanoformulations improves treatment compliance in livestock and companion animals, thereby reducing the workload of managers. Although promising advances have been made, many obstacles remain to be addressed before nanoformulations can be used in a clinical setting. Some crucial issues currently facing this field, including toxicity, quality control, and mass production, are discussed in this review. With the continuous optimization of nanotechnology, polymer-based DDS has shown its potential in reducing antibiotic resistance to veterinary medicines.

Identification of Mycoviruses by dsRNA Extraction.

Mycoviruses exist in all major groups of fungi. With the continuous development of science and technology, the methods of studying viruses are constantly updated, and progressively mycoviruses have been discovered where most of these viruses are RNA viruses. Therefore, double-stranded RNA has traditionally been used as the hallmark of RNA mycovirus detection. This report describes in detail the method of mycovirus identification using extraction of dsRNA. Besides, extraction of viral dsRNA, and the assembly methods of viral genome and identification of virus type are presented.

Epileptic Seizure Detection Based on Path Signature and Bi-LSTM Network With Attention Mechanism.

Automatic seizure detection using electroen-cephalogram (EEG) can significantly expedite the diagnosis of epilepsy, thereby facilitating prompt treatment and reducing the risk of future seizures and associated complications. While most existing EEG-based epilepsy detection studies employ deep learning models, they often ignore the chronological relationships between different EEG channels. To tackle this limitation, a novel automatic epilepsy detection method is proposed, which leverages path signature and Bidirectional Long Short-Term Memory (Bi-LSTM) neural network with an attention mechanism. The path signature algorithm is used to extract discriminative features for capturing the dynamic dependencies between different channels of EEG, while Bi-LSTM with attention further analyzes the inherent temporal dependencies hidden in EEG signal features. Our method is evaluated on two public EEG databases with different sizes (CHB-MIT and TUEP) and a private database from a local hospital. Two experimental settings are used, i.e., five-fold cross-validation and leave-one-out cross-validation. Experimental results show that our method achieves 99.09%, 95.60%, and 99.87% average accuracies on CHB-MIT, TUEP with 250Hz, and TUEP with 256Hz, respectively. On the private dataset, our method also achieves 99.40% average accuracy, which outperforms other methods. Furthermore, our method exhibits robustness in patients, as demonstrated by the evaluation results of cross-patient experiments.

Mitochondria-targeted neutral and cationic iridium(III) anticancer complexes chelating simple hybrid sp2-N/sp3-N donor ligands.

Most platinum group-based cyclometalated neutral and cationic anticancer complexes with the general formula [(C^N)2Ir(XY)]0/+ (neutral complex: XY = bidentate anionic ligand; cationic complex: XY = bidentate neutral ligand) are notable owing to their intrinsic luminescence properties, good cell permeability, interaction with some biomolecular targets and unique mechanisms of action (MoAs). We herein synthesized a series of neutral and cationic amine-imine cyclometalated iridium(III) complexes using Schiff base ligands with sp2-N/sp3-N N^NH2 chelating donors. The cyclometalated iridium(III) complexes were identified by various techniques. They were stable in aqueous media, displayed moderate fluorescence and exhibited affinity toward bovine serum albumin (BSA). The complexes demonstrated promising cytotoxicity against lung cancer A549 cells, cisplatin-resistant lung cancer A549/DDP cells, cervical carcinoma HeLa cells and human liver carcinoma HepG2 cells, with IC50 values ranging from 9.98 to 19.63 µM. Unfortunately, these complexes had a low selectivity (selectivity index: 1.62-1.98) towards A549 cells and BEAS-2B normal cells. The charge pattern of the metal center (neutral or cationic) and ligand substituents showed little influence on the cytotoxicity and selectivity of these complexes. The study revealed that these complexes could target mitochondria, cause depolarization of the mitochondrial membrane, and trigger the production of intracellular ROS. Additionally, the complexes were observed to induce late apoptosis and perturb the cell cycle in the G2/M or S phase in A549 cells. Based on these results, it appears that the anticancer efficacy of these complexes was predominantly attributed to the redox mechanism.

SpyGlass in Diagnosis of Hepatocellular Carcinoma with Right Hepatic Duct Tumor Thrombus Hemorrhage: A Case Report.

Hepatocelluar carcinoma presenting as a biliary duct tumor thrombus is a relatively rare entity, with poor prognosis. The primary clinical manifestation of this disease is obstructive jaundice, which can often be misdiagnosed. A 59-year-old female patient was admitted with sudden onset of abdominal pain. Laboratory tests suggested obstructive jaundice, and enhanced magnetic resonance imaging of the upper abdomen did not show obvious biliary dilatation. Endoscopic ultrasound and endoscopic retrograde cholangiopancreatography suggested an occupying lesion in the upper bile duct. SpyGlass and biopsy finally confirmed hepatocellular carcinoma with right hepatic duct tumor thrombus hemorrhage. The SpyGlass Direct Visualization System, as an advanced biliary cholangioscopy device, showed the advantages of single-person operation as well as easy access to and visualization of the lesion.

Potent Half-Sandwich 16-/18-Electron Iridium(III) and Ruthenium(II) Anticancer Complexes with Readily Available Amine-Imine Ligands.

The synthesis and biological evaluation of stable 16-electron half-sandwich complexes have remained scarce. We herein present the different coordination modes (16-electron or 18-electron) between half-sandwich iridium(III) complexes and ruthenium(II) complexes derived from the same amine-imine ligands chelating hybrid sp3-N/sp2-N donors. The 16-electron iridium(III) and 18-electron ruthenium(II) complexes with different counteranions were obtained and identified by various techniques. The promising cytotoxicity of these complexes against A549 lung cancer cells, cisplatin-resistant A549/DPP cells, cervical carcinoma HeLa cells, and human hepatocellular liver carcinoma HepG2 cells was observed with IC50 values ranging from 5.4 to 16.3 µM. Moreover, these complexes showed a certain selectivity (selectivity index: 2.1-3.7) toward A549 cells and BEAS-2B normal cells. The variation of metal center, counteranion, 16/18-electron coordination mode, and ligand substituents showed little influence on the cytotoxicity and selectivity of these complexes. The mechanism of action study showed that these complexes could target mitochondria, induce the depolarization of the mitochondrial membrane, and promote the generation of intracellular reactive oxygen species (ROS). Further, the induction of cell apoptosis and the perturbation of the cell cycle in the G0/G1 phase were also observed for these complexes. Overall, it seems that the redox mechanism dominated the anticancer efficacy of these complexes.

A novel bipartite negative-stranded RNA mycovirus of the order Bunyavirales isolated from the phytopathogenic fungus Fusarium sibiricum.

A novel negative-stranded RNA mycovirus was isolated from the phytopathogenic fungus Fusarium sibiricum strain AH32. This virus, tentatively named "Fusarium sibiricum coguvirus 1" (FsCV1), has a bipartite genome consisting of two RNA segments (RNA1 and RNA2). The negative-sense RNA1 is 6711 nt in length, encoding the RNA-dependent RNA polymerase (RdRp, p251) in the viral complementary (vc) strand. The ambisense RNA2 (1204 nt long) encodes two proteins from overlapping genes: the nucleocapsid protein (NP, p38) in the vc strand and a protein of unknown function (UFP, p36) in the viral (v) strand. In contrast to other Bunyavirales members, in FsCV1, the two open reading frames are separated by a long AU-rich intergenic region (IR). Sequence comparisons and phylogenetic analysis based on RdRp and NP sequences demonstrated that FsCV1 is a novel bipartite negative-stranded RNA mycovirus of the genus Coguvirus, family Phenuiviridae, order Bunyavirales.

SECP-Net: SE-Connection Pyramid Network for Segmentation of Organs at Risk with Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is a kind of malignant tumor. The accurate and automatic segmentation of computed tomography (CT) images of organs at risk (OAR) is clinically significant. In recent years, deep learning models represented by U-Net have been widely applied in medical image segmentation tasks, which can help to reduce doctors' workload. In the OAR segmentation of NPC, the sizes of the OAR are variable, and some of their volumes are small. Traditional deep neural networks underperform in segmentation due to the insufficient use of global and multi-size information. Therefore, a new SE-Connection Pyramid Network (SECP-Net) is proposed. For extracting global and multi-size information, the SECP-Net designs an SE-connection module and a pyramid structure for improving the segmentation performance, especially that of small organs. SECP-Net also uses an auto-context cascaded structure to further refine the segmentation results. Comparative experiments are conducted between SECP-Net and other recent methods on a private dataset with CT images of the head and neck and a public liver dataset. Five-fold cross-validation is used to evaluate the performance based on two metrics; i.e., Dice and Jaccard similarity. The experimental results show that SECP-Net can achieve SOTA performance in these two challenging tasks.

Characterization of a novel aromatic ring-hydroxylating oxygenase, NarA2B2, from thermophilic Hydrogenibacillus sp. strain N12.

Polycyclic aromatic hydrocarbons (PAHs) are harmful to human health due to their carcinogenic, teratogenic, and mutagenic effects. A thermophilic Hydrogenibacillus sp. strain N12 capable of degrading a variety of PAHs and derivatives was previously isolated. In this study, an aromatic ring-hydroxylating oxygenase, NarA2B2, was identified from strain N12, with substrate specificity including naphthalene, phenanthrene, dibenzothiophene, fluorene, acenaphthene, carbazole, biphenyl, and pyrene. NarA2B2 was proposed to add one or two atoms of molecular oxygen to the substrate and catalyze biphenyl at C-2, 2 or C-3, 4 positions with different characteristics than before. The key catalytic amino acids, H222, H227, and D379, were identified as playing a pivotal role in the formation of the 2-his-1-carboxylate facial triad. Furthermore, we conducted molecular docking and molecular dynamics simulations, notably, D219 enhanced the stability of the iron center by forming two stable hydrogen bonds with H222, while the mutation of F216, T223, and H302 modulated the catalytic activity by altering the pocket's size and shape. Compared to the wild-type (WT) enzyme, the degradation ratios of acenaphthene by F216A, T223A, and H302A had an improvement of 23.08%, 26.87%, and 29.52%, the degradation ratios of naphthalene by T223A and H302A had an improvement of 51.30% and 65.17%, while the degradation ratio of biphenyl by V236A had an improvement of 77.94%. The purified NarA2B2 was oxygen-sensitive when it was incubated with L-ascorbic acid in an anaerobic environment, and its catalytic activity was restored in vitro. These results contribute to a better understanding of the molecular mechanism responsible for PAHs' degradation in thermophilic microorganisms.IMPORTANCE(i) A novel aromatic ring-hydroxylating oxygenase named NarA2B2, capable of degrading multiple polycyclic aromatic hydrocarbons and derivatives, was identified from the thermophilic microorganism Hydrogenibacillus sp. N12. (ii) The degradation characteristics of NarA2B2 were characterized by adding one or two atoms of molecular oxygen to the substrate. Unlike the previous study, NarA2B2 catalyzed biphenyl at C-2, 2 or C-3, 4 positions. (iii) Catalytic sites of NarA2B2 were conserved, and key amino acids F216, D219, H222, T223, H227, V236, F243, Y300, H302, W316, F369, and D379 played pivotal roles in catalysis, as confirmed by protein structure prediction, molecular docking, molecular dynamics simulations, and point mutation.

Half-Sandwich Iridium(III), Rhodium(III), and Ruthenium(II) Complexes Chelating Hybrid sp2-N/sp3-N Donor Ligands to Achieve Improved Anticancer Selectivity.

The biological efficacy of half-sandwich platinum group organometallic complexes of the formula [(η5-Cpx)/(η6-arene)M(XY)Cl]0/+ (XY = bidentate ligands; Cpx = functionalized cyclopentadienyl; M = Ir, Rh, Ru, Os) has received considerable attention due to the significance of the metal center, chelating ligand, and Cpx/arene moieties in defining their anticancer potency and selectivity. With a facile access to the BIAN-derived imine-amine ligands using alkylaluminum as the reductant, we herein described the preparation and characterization of 16 half-sandwich Ir(III), Rh(III), and Ru(II) complexes chelating the hybrid sp2-N/sp3-N donor ligand. A nonplanar five-member metallacycle was confirmed by X-ray single-crystal structures of Ir1-Ir3, Ir7, Rh1, Ru1, and Ru4. The attempt to prepare imine-amido complexes using a base as the deprotonating agent led to the mixture of imine-amine complexes, within which the leaving group Cl- was displaced, and 16-electron imine-amido complexes without Cl-. The half-sandwich imine-amine complexes in this system underwent rapid hydrolysis in aqueous solution, exhibited weak photoluminescence, and showed the ability of binding to CT-DNA and BSA. The cytotoxicity of all imine-amine complexes against A549 lung cancer cell lines, HeLa cervical cancer cell lines, and 4T1 mouse breast cancer cells was determined by an MTT assay. The IC50 values of these complexes were in a range of 5.71-67.28 µM. Notably, most of these complexes displayed improved selectivity toward A549 cancer cells versus noncancerous BEAS-2B cells in comparison with the corresponding α-diimine complexes chelating the sp2-N/sp2-N donor ligand, which have been shown no selectivity in our previous report. The anticancer selectivity of these complexes appeared to be related to the redox-based mechanism including the catalytic oxidation of NADH to NAD+, reactive oxygen species (ROS) generation, and depolarization of the mitochondrial membrane. Further, inducing apoptosis of these complexes in A549 cancer cells and BEAS-2B normal cells also correlated with their anticancer selectivity, indicating the apoptosis mode of cell death in this system. In addition, these complexes could enter A549 cells via energy-dependent pathway and were able to impede the in vitro migration of A549 cells.

A phthalocyanine-based porous organic polymer for a lithium-ion battery anode.

Porous organic polymers (POPs) are a novel class of polymeric materials with high flexibility and designability for building structures. Herein, a phthalocyanine-based porous organic polymer (PcPOP) was constructed in situ on copper foil from H2Pc(ethynyl)4 [Pc(ethynyl)4 = 2(3),9(10),16(17),23(24)-tetra(ethynyl)phthalocyanine] by the coupling reaction. Benefiting from the uniformly distributed electron-rich nitrogen atoms in the Pc structure and the sp-hybridized carbons in the acetylenic linkage, Li intercalation in the porous organic polymer would be improved and stabilized. As a result, PcPOP showed remarkable electrochemical performance in lithium-ion batteries as the anode, including high specific capacity (a charge capacity of 1172 mA h g-1 at a current density of 150 mA g-1) and long cycling stability (a reversible capacity of 960.1 mA h g-1 can be achieved even after 600 cycles at a current density of 1500 mA g-1). The result indicates that the intrinsic doping of electron-rich sites of the building molecules is beneficial for the electrochemical performance of the porous organic polymer.

Diversity of Lasiodiplodia species associated with canker and dieback in fruit trees from the Henan and Shandong provinces of China.

Lasiodiplodia is a widely distributed genus that is associated with a variety of diseases on many plant species, especially fruit trees. The current study conducted a disease survey of fruit trees growing in 12 orchards located within the Henan and Shandong provinces of China between 2020 and 2022. The symptoms observed included stem canker, branch dieback, and gummosis. Phylogenetic analyses of internal transcribed spacer (ITS), tub2, tef1, and rpb2 sequence data combined with morphological characteristics, revealed that the 19 isolates collected during the survey belonged to five documented Lasiodiplodia species, including Lasiodiplodia citricola, L. chiangraiensis, L. huangyanensis, L. pseudotheobromae, and L. theobromae, as well as two previously undescribed species, L. xinyangensis and L. ziziphi. In addition, the survey identified three novel host/pathogen interactions including L. chiangraiensis on loquat, L. citricola on apple, and L. huangyanensis on grapevine. Furthermore, the detailed phylogenic analysis indicated that four previously described Lasiodiplodia species were so closely related genetically that they would be better classified as synonyms rather than distinct species, so L. paraphysoides and L. nanpingensis should be considered synonyms of L. citricola, and that L. fujianensis should be a synonym of L. iraniensis, and L. henanica a synonym of L. huangyanensis. Pathogenicity tests confirmed that representative isolates of the two novel species and three new host/pathogen interactions identified in the current study were pathogenic to their original hosts, and fulfilled Koch's postulates. Similarly, all of the isolates were found to be pathogenic on four alternative hosts, although a high degree of variation in virulence was observed.

Clinical significance and potential application of cuproptosis-related genes in gastric cancer.

BACKGROUND: Worldwide, gastric cancer (GC) is a common lethal solid malignancy with a poor prognosis. Cuproptosis is a novel type of cell death mediated by protein lipoylation and may be related to GC prognosis. AIM: To offer new insights to predict GC prognosis and provide multiple therapeutic targets related to cuproptosis-related genes (CRGs) for future therapy. METHODS: We collected data from several public data portals, systematically estimated the expression level and prognostic values of CRGs in GC samples, and investigated related mechanisms using public databases and bioinformatics. RESULTS: Our results revealed that FDX1, LIAS, and MTF1 were differentially expressed in GC samples and exhibited important prognostic significance in The Cancer Genome Atlas (TCGA) cohort. We constructed a nomogram model for overall survival and disease-specific survival prediction and validated it via calibration plots. Mecha-nistically, immune cell infiltration and DNA methylation prominently affected the survival time of GC patients. Moreover, protein-protein interaction network, KEGG pathway and gene ontology enrichment analyses demonstrated that FDX1, LIAS, MTF1 and related proteins play key roles in the tricarboxylic acid cycle and cuproptosis. Gene Expression Omnibus database validation showed that the expression levels of FDX1, LIAS, and MTF1 were consistent with those in the TCGA cohort. Top 10 perturbagens has been filtered by Connectivity Map. CONCLUSION: In conclusion, FDX1, LIAS, and MTF1 could serve as potential prognostic biomarkers for GC patients and provide novel targets for immunotarget therapy.

A Mycovirus VIGS Vector Confers Hypovirulence to a Plant Pathogenic Fungus to Control Wheat FHB.

Mycovirus-mediated hypovirulence has the potential to control fungal diseases. However, the availability of hypovirulence-conferring mycoviruses for plant fungal disease control is limited as most fungal viruses are asymptomatic. In this study, the virus-induced gene silencing (VIGS) vector p26-D4 of Fusarium graminearum gemytripvirus 1 (FgGMTV1), a tripartite circular single-stranded DNA mycovirus, is successfully constructed to convert the causal fungus of cereal Fusarium head blight (FHB) into a hypovirulent strain. p26-D4, with an insert of a 75-150 bp fragment of the target reporter transgene transcript in both sense and antisense orientations, efficiently triggered gene silencing in Fusarium graminearum. Notably, the two hypovirulent strains, p26-D4-Tri101, and p26-D4-FgPP1, obtained by silencing the virulence-related genes Tri101 and FgPP1 with p26-D4, can be used as biocontrol agents to protect wheat from a fungal disease FHB and mycotoxin contamination at the field level. This study not only describes the first mycovirus-derived VIGS system but also proves that the VIGS vector can be used to establish multiple hypovirulent strains to control pathogenic fungi.

A cell-electrode interface signal-to-noise ratio model for 3D micro-nano electrode.

Objective. Three-dimensional micro-nano electrodes (MNEs) with the vertical nanopillar array distributed on the surface play an increasingly important role in neural science research. The geometric parameters of the nanopillar array and the cell adhesion state on the nanopillar array are the factors that may affect the MNE recording. However, the quantified relationship between these parameters and the signal-to-noise ratio (SNR) is still unclear. This paper establishes a cell-MNE interface SNR model and obtains the mathematical relationship between the above parameters and SNR.Approach. The equivalent electrical circuit and numerical simulation are used to study the sensing performance of the cell-electrode interface. The adhesion state of cells on MNE is quantified as engulfment percentage, and an equivalent cleft width is proposed to describe the signal loss caused by clefts between the cell membrane and the electrode surface.Main results. Whether the planar substrate is insulated or not, the SNR of MNE is greater than planar microelectrode only when the engulfment percentage is greater than a certain value. Under the premise of maximum engulfment percentage, the spacing and height of nanopillars should be minimized, and the radius of the nanopillar should be maximized for better signal quality.Significance. The model can clarify the mechanism of improving SNR by nanopillar arrays and provides the theoretical basis for the design of such nanopillar neural electrodes.

Nova proteins direct synaptic integration of somatostatin interneurons through activity-dependent alternative splicing.

Somatostatin interneurons are the earliest born population of cortical inhibitory cells. They are crucial to support normal brain development and function; however, the mechanisms underlying their integration into nascent cortical circuitry are not well understood. In this study, we begin by demonstrating that the maturation of somatostatin interneurons in mouse somatosensory cortex is activity dependent. We then investigated the relationship between activity, alternative splicing, and synapse formation within this population. Specifically, we discovered that the Nova family of RNA-binding proteins are activity-dependent and are essential for the maturation of somatostatin interneurons, as well as their afferent and efferent connectivity. Within this population, Nova2 preferentially mediates the alternative splicing of genes required for axonal formation and synaptic function independently from its effect on gene expression. Hence, our work demonstrates that the Nova family of proteins through alternative splicing are centrally involved in coupling developmental neuronal activity to cortical circuit formation.

Association between multimorbidity and falls and fear of falling among older adults in eastern China: a cross-sectional study.

Background: Growing evidence has reported an association between multimorbidity and falls and fear of falling (FOF) in older adults, however, the results regarding this association from China are limited. Our study aimed to investigate the association between multimorbidity and falls and FOF in older adults in eastern China. Methods: We conducted a cross-sectional study in Zhejiang Province, Eastern China, which recruited a provincial representative sample of adults aged ≥ 60 years. A structured questionnaire including demographic characteristics, chronic diseases, history of falls in the past 12 months, and FOF, was administered by all participants. The exposure variable was multimorbidity, which was defined as the presence of two or more chronic diseases and medical conditions in the same individual. The outcomes included a history of falls and FOF. Multivariate logistic regression was used to evaluate the association between multimorbidity and falls and FOF in older adults. Results: In total of 7,774 participants were included in the analysis, among whom 3,898 (50.1%) were female, with a mean ± standard deviation age is 72.9 ± 8.4 years. Multimorbidity was associated with the increased risk of falling in older adults [adjusted odds ratio (OR), 1.99; 95% confidence interval (CI):1.55-2.36]. The ORs for having experienced single fall and repeated falls were 1.85 (95% CI: 1.42-2.42) and 3.45 (95% CI: 1.47-6.97), respectively, with multimorbidity compared with those without chronic diseases. The older adults with multimorbidity were more likely to report FOF compared with those without chronic diseases (adjusted OR, 1.49; 95%CI:1.30-1.70). Moreover, the association between multimorbidity and FOF remained significant in the older adults with a history of fall (OR, 1.57; 95%CI:1.04-2.38). Conclusion: The association between multimorbidity and falls and FOF is significant in the Chinese population and the effects of multimorbidity on falls and FOF do not vary according to the frequency and history of falls in older adults.