High Performance Nacre Fibers by Engineering Interfacial Entanglement.

Biological materials exhibit fascinating mechanical properties for intricate interactions at multiple interfaces to combine superb toughness with wondrous strength and stiffness. Recently, strong interlayer entanglement has emerged to replicate the powerful dissipation of natural proteins and alleviate the conflict between strength and toughness. However, designing intricate interactions in a strong entanglement network needs to be further explored. Here, we modulate interlayer entanglement by introducing multiple interactions, including hydrogen and ionic bonding, and achieve ultrahigh mechanical performance of graphene-based nacre fibers. Two essential modulating trends are directed. One is modulating dynamic hydrogen bonding to improve the strength and toughness up to 1.58 GPa and 52 MJ/m3, simultaneously. The other is tailoring ionic coordinating bonding to raise the strength and stiffness, reaching 2.3 and 253 GPa. Modulating various interactions within robust entanglement provides an effective approach to extend performance limits of bioinspired nacre and optimize multiscale interfaces in diverse composites.

Complete Mitogenome sequencing of the fish louse Argulus japonicus (Crustacea: Branchiura): Comparative analyses and phylogenetic implications.

The fish louse Argulus japonicus, a branchiuran crustacean of the Argulidae family, is attracting increasing attention because of its parasitic tendencies and significant health threats to global fish farming. The mitogenomes can yield a foundation for studying epidemiology, genetic diversity, and molecular ecology and therefore may be used to assist in the surveillance and control of A. japonicus. In this study, we sequenced and assembled the complete mitogenome of A. japonicus to shed light on its genetic and evolutionary blueprint. Our investigation indicated that the 15,045-bp circular genome of A. japonicus encodes 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), and 2 ribosomal RNAs (rRNAs) with significant AT and GC skews. Comparative genomics provided an evolutionary scenario for the genetic diversity of 13 PCGs: all were under purifying selection, with cox1 and nad6 having the lowest and highest evolutionary rates, respectively. Genome-wide phylogenetic trees established a close relationship between species of the families Argulidae (Arguloida) and Armilliferidae (Porocephalida) within Crustacea, and further, A. japonicus and Argulus americanus were determined to be more closely related to each other than to others within the family Argulidae. Single PCG-based phylogenies supported nad1 and nad6 as the best genetic markers for evolutionary and phylogenetic studies for branchiuran crustaceans due to their similar phylogenetic topologies with those of genome-based phylogenetic analyses. To sum up, these comprehensive mitogenomic data of A. japonicus and related species refine valuable marker resources and should contribute to molecular diagnostic methods, epidemiological investigations, and ecological studies of the fish ectoparasites in Crustacea.

Design, synthesis, and antiviral activity of 1-aryl-4-arylmethylpiperazine derivatives as Zika virus inhibitors with broad antiviral spectrum.

Zika virus (ZIKV) disease has been given attention due to the risk of congenital microcephaly and neurodevelopmental disorders after ZIKV infection in pregnancy, but no vaccine or antiviral drug is available. Based on a previously reported ZIKV inhibitor ZK22, a series of novel 1-aryl-4-arylmethylpiperazine derivatives was designed, synthesized, and investigated for antiviral activity by quantify cellular ZIKV RNA amount using RT-qPCR method in ZIKV-infected human venous endothelial cells (HUVECs) assay. Structure-activity relationship (SAR) analysis demonstrated that anti-ZIKV activity of 1-aryl-4-arylmethylpiperazine derivatives is not correlated with molecular hydrophobicity, multiple new derivatives with pyridine group to replace the benzonitrile moiety of ZK22 showed stronger antiviral activity, higher ligand lipophilicity efficiency as well as lower cytotoxicity. Two active compounds 13 and 33 were further identified as novel ZIKV entry inhibitors with the potential of oral available. Moreover, both ZK22 and newly active derivatives also possess of obvious inhibition on the viral replication of coronavirus and influenza A virus at low micromolar level. In summary, this work provided better candidates of ZIKV inhibitor for preclinical study and revealed the promise of 1-aryl-4-arylmethylpiperazine chemotype in the development of broad-spectrum antiviral agents.

Emerging Landscape of Supercharged Proteins and Peptides for Drug Delivery.

Although groundbreaking biotechnological techniques such as gene editing have significantly progressed, the effective and targeted transport of therapeutic agents into host cells remains a major obstacle to the development of biotherapeutics. Confronting the unique challenge posed by large macromolecules such as proteins, peptides, and nucleic acids adds complexity to this issue. Recent findings reveal that the supercharging of proteins and peptides not only enables control over critical properties, such as temperature resistance and catalytic activity, but also holds promise as a viable strategy for their use in drug delivery. This review provides a concise summary of the attributes of supercharged proteins and peptides, encompassing both their natural occurrence and engineered variants. Furthermore, it sheds light on the present status and future possibilities of supercharged proteins and peptides as carriers for significant biomolecules in the realms of medical research and therapeutic applications.

A cell-based assay to discover inhibitors of Zika virus RNA-dependent RNA polymerase.

Zika virus (ZIKV) belongs to Flaviviridae, the Flavivirus genus. Its infection causes congenital brain abnormalities and Guillain-Barré syndrome. However, there are no effective vaccines, no FDA-approved drugs to manage ZIKV infection. The non-structural protein NS5 of ZIKV has been recognized as a valuable target of antivirals because of its RNA-dependent RNA polymerase (RdRp) and methyltransferase (MTase) activities essential for viral RNA synthesis. Here, we report a cell-based assay for discovering inhibitors of ZIKV NS5 and found that 5-Azacytidine potently inhibits ZIKV NS5, with EC50 of 4.9 µM. Furthermore, 5-Azacytidine suppresses ZIKV replication by inhibiting NS5-mediated viral RNA transcription. Therefore, we have developed a cell-based ZIKV NS5 assay which can be deployed to discover ZIKV NS5 inhibitors and demonstrated the potential of 5-Azacytidine for further development as a ZIKV NS5 inhibitor.

Multimorbidity, cognitive phenotypes, and Alzheimer's disease plasma biomarkers in older adults: A population-based study.

INTRODUCTION: To examine the burden and clusters of multimorbidity in association with mild cognitive impairment (MCI), dementia, and Alzheimer's disease (AD)-related plasma biomarkers among older adults. METHODS: This population-based study included 5432 participants (age ≥60 years); of these, plasma amyloid beta (Aß), total tau, and neurofilament light chain (NfL) were measured in a subsample (n = 1412). We used hierarchical clustering to generate five multimorbidity clusters from 23 chronic diseases. We diagnosed dementia and MCI following international criteria. Data were analyzed using logistic and linear regression models. RESULTS: The number of chronic diseases was associated with dementia (multivariable-adjusted odds ratio = 1.22; 95% confidence interval [CI] = 1.11 to 1.33), AD (1.13; 1.01 to 1.26), vascular dementia (VaD) (1.44; 1.25 to 1.64), and non-amnestic MCI (1.25; 1.13 to 1.37). Metabolic cluster was associated with VaD and non-amnestic MCI, whereas degenerative ocular cluster was associated with AD (p < 0.05). The number of chronic diseases was associated with increased plasma Aß and NfL (p < 0.05). DISCUSSION: Multimorbidity burden and clusters are differentially associated with subtypes of dementia and MCI and AD-related plasma biomarkers in older adults. HIGHLIGHTS: We used hierarchical clustering to generate five clusters of multimorbidity. The presence and load of multimorbidity were associated with dementia and mild cognitive impairment. Multimorbidity clusters were differentially associated with subtypes of dementia and Alzheimer's disease plasma biomarkers.

Diagnosis of Potomac horse fever (syn. equine neorickettsiosis) in 2 foals in southwestern Ontario.

Potomac horse fever (PHF) is characterized by fever, depression, anorexia, ileus, diarrhea, and occasionally, laminitis. The disease is caused by infection with Neorickettsia risticii and/or N. findlayensis. Equids of all ages may be affected; however, the condition has not been well-characterized in foals. This report describes clinical signs, laboratory findings, and treatment of 2 foals diagnosed with PHF in southwestern Ontario. Feces submitted for an equine PCR panel tested positive for Neorickettsia spp. and were subsequently confirmed to be N. risticii (Case 1) and N. findlayensis (Case 2). Both foals recovered following hospitalization and intensive care. Key clinical message: The purpose of this report is to make veterinarians aware that foals may develop PHF. During summer (July to September), when encountering foals in endemic areas with clinical signs compatible with PHF, veterinarians should consider PHF as a diagnostic rule-out. For confirmation of the diagnosis, blood and feces should be submitted for PCR testing for Neorickettsia spp.

Diagnostic de la fièvre équine du Potomac (syn. néorickettsiose équine) chez 2 poulains dans le sud-ouest de l'Ontario. La fièvre équine du Potomac (PHF) se caractérise par de la fièvre, une dépression, de l'anorexie, un iléus, de la diarrhée et, occasionnellement, une fourbure. La maladie est causée par une infection par Neorickettsia risticii et/ou N. findlayensis. Les équidés de tous âges peuvent être atteints; cependant, cette pathologie n'a pas été bien caractérisée chez les poulains. Ce rapport décrit les signes cliniques, les résultats de laboratoire et le traitement de 2 poulains diagnostiqués avec PHF dans le sud-ouest de l'Ontario. Les matières fécales soumises à un panel PCR équin se sont révélées positives pour Neorickettsia spp. et ont ensuite été confirmées comme étant positives pour N. risticii (cas 1) et N. findlayensis (cas 2). Les deux poulains se sont rétablis après une hospitalisation et des soins intensifs.Message clinique clé :Le but de ce rapport est de sensibiliser les vétérinaires au fait que les poulains peuvent développer une PHF. Pendant l'été (juillet à septembre), lorsqu'ils rencontrent des poulains dans des zones d'endémie présentant des signes cliniques compatibles avec le PHF, les vétérinaires doivent considérer le PHF comme une exclusion diagnostique. Pour confirmer le diagnostic, du sang et des selles doivent être soumis à un test PCR pour Neorickettsia spp.(Traduit par Dr Serge Messier).

Full hardware implementation of neuromorphic visual system based on multimodal optoelectronic resistive memory arrays for versatile image processing.

In-sensor and near-sensor computing are becoming the next-generation computing paradigm for high-density and low-power sensory processing. To fulfil a high-density and efficient neuromorphic visual system with fully hierarchical emulation of the retina and visual cortex, emerging multimodal neuromorphic devices for multi-stage processing and a fully hardware-implemented system with versatile image processing functions are still lacking and highly desirable. Here we demonstrate an emerging multimodal-multifunctional resistive random-access memory (RRAM) device array based on modified silk fibroin protein (MSFP), exhibiting both optoelectronic RRAM (ORRAM) mode featured by unique negative and positive photoconductance memory and electrical RRAM (ERRAM) mode featured by analogue resistive switching. A full hardware implementation of the artificial visual system with versatile image processing functions is realised for the first time, including ORRAM mode array for the in-sensor image pre-processing (contrast enhancement, background denoising, feature extraction) and ERRAM mode array for near-sensor high-level image recognition, which hugely improves the integration density, and simply the circuit design and the fabrication and integration complexity.

A case report of huge pancreas mucinous cystic neoplasm during pregnancy: How doctors think.

RATIONALE: Pancreas mucinous cystic neoplasm (PMCN) is uncommon, and its occurrence during pregnancy is rare. The management of PMCN during pregnancy, including diagnosis and surgical timing, is a great challenge. PATIENT CONCERNS: A nontender epigastric mass of the upper abdomen was detected by palpation in a 35-year-old woman, gravida 2, para 1, during the 36th week of gestation. She was referred to our institution for further evaluation. DIAGNOSES: Magnetic resonance imaging (MRI) showed a multilocular cystic mass in the body and tail of the pancreas (16.7/12.1/17.6 cm), well-circumscribed with a hyper signal on T2-weighted MRI images. The diagnosis of a pancreatic cyst, probable mucinous, was established. INTERVENTIONS: The patient was informed of the possibilities of malignancy, rapid growth, and rupture of the tumor. After a laparotomy and cesarean section, a large cystic tumor was discovered adherent to the pancreas, spleen, mesocolon, and retroperitoneum. The spleen was preserved since there was no evidence of invasion. According to macroscopic examinations, the tumor measured 18 cm was filled with a dark yellow-brownish mucinous fluid and did not appear to communicate with the pancreatic ducts. OUTCOMES: After six months of follow-up, there were no signs of recurrence in the patient. LESSONS: PMCN may need to be surgically resected in cases characterized by malignancy risk during pregnancy. As female sex hormones may influence the behavior of PMCN during pregnancy, surgical timing should be determined based on the stage of pregnancy, malignancy status, and condition of the mother and fetus.

Generative complex networks within a dynamic memristor with intrinsic variability.

Artificial neural networks (ANNs) have gained considerable momentum in the past decade. Although at first the main task of the ANN paradigm was to tune the connection weights in fixed-architecture networks, there has recently been growing interest in evolving network architectures toward the goal of creating artificial general intelligence. Lagging behind this trend, current ANN hardware struggles for a balance between flexibility and efficiency but cannot achieve both. Here, we report on a novel approach for the on-demand generation of complex networks within a single memristor where multiple virtual nodes are created by time multiplexing and the non-trivial topological features, such as small-worldness, are generated by exploiting device dynamics with intrinsic cycle-to-cycle variability. When used for reservoir computing, memristive complex networks can achieve a noticeable increase in memory capacity a and respectable performance boost compared to conventional reservoirs trivially implemented as fully connected networks. This work expands the functionality of memristors for ANN computing.

The mitogenomes characterization of two Peltigera species (Peltigera elisabethae and Peltigera polydactylon) and comparative mitogenomic analyses of six Peltigera.

In the present study, the mitochondrial genomes of Peltigera elisabethae and P. polydactylon were sequenced and assembled. The two mitogenomes were composed of circular DNA molecules, with sizes of 64,034 bp and 59,208 bp, respectively. Comparative analysis showed that the genome size, GC content, GC skew, and AT skew varied between the two mitochondrial genomes. In codon analysis, phenylalanine (Phe), isoleucine (Ile), and leucine (Leu) were most frequently used in six Peltigera genomes. Evolutionary analysis showed that all 14 protein-coding genes (PCGs) were subject to purifying selection in the six Peltigera species. Regarding gene rearrangement, the PCGs of Peltigera had the same gene sequence and gene content, and a few intron sequences and spacer sequences were rearranged in Peltigera. In the phylogenetic analysis, we used Bayesian and ML methods to construct a phylogenetic tree. Two phylogenetic trees with consistent topology with high support indicate that mitochondrial genes were reliable molecular markers for analyzing the phylogenetic relationships. The present study enriches the mitochondrial genome data of Peltigera and promotes further understanding of the genetics and evolution of the Peltigera genus.

Impacts of Eimeria coinfection on growth performance, intestinal health and immune responses of broiler chickens.

Coccidiosis caused by Eimeria is one of the most severe chicken diseases and imposes huge economic losses to the poultry industry globally. Multi-Eimeria species coinfections are common with the most prevalent combination being mixtures of Eimeria acervulina and Eimeria tenella. Although detrimental impacts of either E. acervulina or E. tenella on chicken health are well recognized, no information is available regarding their coinfection effects so far. This study was designed to investigate the influence of coinfection with E. acervulina and E. tenella on broiler chickens. 144 one-day-old broiler chickens within each of trials (trial I or II) were divided into four groups, namely, control group (CG), E. acervulina infection group (EAIG), E. tenella infection group (ETIG) and dual (E. acervulina and E. tenella) infection group (DIG). Then, chickens were measured for weight loss, lesion scores, oocyst outputs, histological changes and expressions of pro-inflammatory (interleukin [IL]-6, IL-8 and IL-18), regulatory (IL-10 and IL-22) cytokines and Toll-like receptors (TLR; TLR2 and TLR4) as well as intestinal barrier (mucin 2 [MUC2] and fattey acid-bingding proteins 2 and 6 [FABP2 and FABP6])- and tight junction (TJ; zonula occluden-1 [ZO-1], occludin [OCLN], and claudins 1 and 5 [CLDN1 and CLDN5])-related proteins at 3, 5, 7, 10, 14 and 21 days post-infection, respectively. Our results consistently showed that although ETIG and DIG exhibited a higher level of weight loss and a more amount of oocyst excretion than EAIG, DIG had lighter lesions than EAIG in the early phase because of coinfection with E. tenella. A higher (P < 0.05) ratio of duodenal villous height to crypt depth was also observed in DIG than EAIG. Moreover, histological changes in the duodenum and cecum varied by single and dual Eimeria infections. Expressions of the intestinal barrier- and TJ-related genes of EAIG, ETIG and DIG were significantly (P < 0.05) upregulated but their levels exhibited differential changes among infected chickens. Similarly, the infected chickens showed significant (P < 0.05) inflammatory responses and higher (P < 0.05) expressions of TLRs in the intestines in comparison to CG. These results presented a comprehensive physiological, pathological and immunological characterization of E. acervulina and E. tenella coinfection in broiler chickens and also shed insights into pathogenesis of multi-coccidia coinfections.

Eimeria zuernii (Eimeriidae: Coccidia): mitochondrial genome and genetic diversity in the Chinese yak.

BACKGROUND: Coccidiosis caused by Eimeria zuernii (Eimeriidae: Coccidia) represents a significant economic threat to the bovine industry. Understanding the evolutionary and genetic biology of E. zuernii can assist in new interaction developments for the prevention and control of this protozoosis. METHODS: We defined the evolutionary and genetic characteristics of E. zuernii by sequencing the complete mitogenome and analyzing the genetic diversity and population structure of 51 isolates collected from eight yak breeding parks in China. RESULTS: The 6176-bp mitogenome of E. zuernii was linear and encoded typical mitochondrial contents of apicomplexan parasites, including three protein-coding genes [PCGs; cytochrome c oxidase subunits I and III (cox1 and cox3), and cytochrome b (cytb)], seven fragmented small subunit (SSU) and 12 fragmented large subunit (LSU) rRNAs. Genome-wide comparative and evolutionary analyses showed cytb and cox3 to be the most and least conserved Eimeria PCGs, respectively, and placed E. zuernii more closely related to Eimeria mephitidis than other Eimeria species. Furthermore, cox1-based genetic structure defined 24 haplotypes of E. zuernii with high haplotype diversities and low nucleotide diversities across eight geographic populations, supporting a low genetic structure and rapid evolutionary rate as well as a previous expansion event among E. zuernii populations. CONCLUSIONS: To our knowledge, this is the first study presenting the phylogeny, genetic diversity, and population structure of the yak E. zuernii, and such information, together with its mitogenomic data, should contribute to a better understanding of the genetic and evolutionary biological studies of apicomplexan parasites in bovines.

A double-cycle echo state network topology for time series prediction.

Echo state network (ESN) has gained wide acceptance in the field of time series prediction, relying on sufficiently complex reservoir connections to remember the historical features of the data and using these features to obtain the outputs by a simple linear readout. However, the randomness of its input and reservoir connections pose negative impacts on the prediction performance and performance stability of the models, the complexity of reservoir connections brings high time consumption during network computing, and the presence of randomness and complexity makes the hardware implementation of the ESN difficult. In response, we propose a double-cycle ESN (DCESN) based on the Li-ESN model, which has fixed weights to improve prediction performance and performance stability and simpler reservoir connections compared to the classical ESN to reduce the time consumption. The existence of both greatly reduces the difficulty of hardware implementation of the ESN and provides many conveniences for the future application of the ESN. Experimental results on many widely used time series datasets show that the DCESN has comparable or even better prediction performance than the ESN and good robustness against noise and parameter fluctuations.

Falling-Leaves Stacking Aggregation of Two-Dimensional Macromolecular Graphene Oxide in Solution.

Understanding the dynamical behaviors of two-dimensional (2D) macromolecules is of fundamental importance for the precise modulation of their assembled structures and material performances. However, considerably less is known about how discrete macromolecular sheets aggregate into extended macroscopic assemblies in solutions. The absence of a quantitative description of the assembly process limits the precise structural control of assemblies. Here, we investigated the aggregation thermodynamic transition and kinetic behavior of 2D macromolecules in the model of single layer graphene oxide (GO). Combining Flory-Huggins theory with experimental observations, we unveiled the critical thermodynamic transition of GO to correlate with the solvent property. We proposed a theoretical falling-leaf model to quantitatively describe the kinetic aggregation process of 2D GO sheets. Experimental analysis validated the theoretical prediction that the thickness of GO aggregates has a power law relation with the poor solvent content. Our work provides a fundamental understanding of phase separation of 2D macromolecules and offers an insight into modulating the aggregated structures of their assembled materials.

Delivery of Oleanolic Acid with Improved Antifibrosis Efficacy by a Cell Penetrating Peptide P10.

Oleanolic acid (OA), a common pentacyclic triterpenoid found in plants, has several therapeutic uses, including the treatment of hepatopathy disorders. However, due to OA's weak permeability and limited bioavailability, its therapeutic advantages are limited. Here, we showed that a short peptide known as p10 not only binds to OA but also rapidly enhances OA delivery into cultured hepatic stellate cells (HSCs), lowers their synthesis of fibrogenic proteins, and further reduces the HSC migration capacity. Our findings show that noncovalently conjugating short peptides to OA improves its pharmacological efficacy and permeability.

Mn3O4 Nanozyme Loaded Thermosensitive PDLLA-PEG-PDLLA Hydrogels for the Treatment of Inflammatory Bowel Disease.

When reactive oxygen species (ROS) accumulate in the body, they can lead to inflammatory bowel disease (IBD) through their oxidative damages to DNA, proteins, and lipids. In this study, a thermosensitive hydrogel-based nanozyme was developed to treat IBD. We first synthesized a manganese oxide (Mn3O4) nanozyme with multienzyme activity followed by physically loading with a thermosensitive hydrogel poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide)-based triblock copolymer (PDLLA-PEG-PDLLA). Then, a mouse model based on the inducement of dextran sulfate sodium (DSS) was built to assess the ROS targeting, scavenging, as well as anti-inflammatory ability of Mn3O4 nanozymes-loaded PDLLA-PEG-PDLLA (MLPPP). Because of the sharp gelation behavior of PDLLA-PEG-PDLLA in body temperature, the MLPPP nanozyme can easily target the inflamed colon after colorectal administration. Following the formation of a physical protection barrier and sustained release of manganese oxide nanozymes that had diverse enzymatic activities and can effectively scavenge ROS, the administration of the MLPPP nanozyme had a high efficacy for treating colitis mice; importantly, after the treatment with this novel nanoformulation, the levels of the pathological indicators in colons as well as in sera of colitis mice were even comparable to healthy mice. Therefore, the MLPPP nanozyme has a potential application for nanotherapy of IBD and would have great clinical translation prospects.

Identification of the hub genes in polycystic ovary syndrome based on disease-associated molecule network.

Revealing the key genes involved in polycystic ovary syndrome (PCOS) and elucidating its pathogenic mechanism is of extreme importance for the development of targeted clinical therapy for PCOS. Investigating disease by integrating several associated and interacting molecules in biological systems will make it possible to discover new pathogenic genes. In this study, an integrative disease-associated molecule network, combining protein-protein interactions and protein-metabolites interactions (PPMI) network was constructed based on the PCOS-associated genes and metabolites systematically collected. This new PPMI strategy identified several potential PCOS-associated genes, which have unreported in previous publications. Moreover, the systematic analysis of five benchmarks data sets indicated the DERL1 was identified as downregulated in PCOS granulosa cell and has good classification performance between PCOS patients and healthy controls. CCR2 and DVL3 were upregulated in PCOS adipose tissues and have good classification performance. The expression of novel gene FXR2 identified in this study is significantly increased in ovarian granulosa cells of PCOS patients compared with controls via quantitative analysis. Our study uncovers substantial differences in the PCOS-specific tissue and provides a plethora of information on dysregulated genes and metabolites that are linked to PCOS. This knowledgebase could have the potential to benefit the scientific and clinical community. In sum, the identification of novel gene associated with PCOS provides valuable insights into the underlying molecular mechanisms of PCOS and could potentially lead to the development of new diagnostic and therapeutic strategies.

Prevalence and Progression of Subjective Cognitive Decline Among Rural Chinese Older Adults: A Population-Based Study.

BACKGROUND: Few community-based studies have examined occurrence and progression of subjective cognitive decline (SCD). OBJECTIVE: To investigate prevalence and progression of SCD among rural-dwelling Chinese elderly people. METHODS: This cohort study included 2,488 cognitively unimpaired adults (age≥65 years) who were examined at baseline (2014-2015) and followed in 2018. Demographic, epidemiological, clinical, and neuropsychological data were collected via in-person interviews and clinical examinations following a structured questionnaire. At baseline, SCD was assessed using the self-rated Ascertain Dementia 8-item Questionnaire. At follow-up, Alzheimer's disease (AD) and vascular dementia (VaD) were clinically diagnosed following the international criteria. Data were analyzed using logistic regression models. RESULTS: The prevalence of SCD was 40.07%. SCD at baseline was associated with the multivariable-adjusted odds ratio (OR) of 1.51 (95% confidence interval 1.10-2.07) for incident cognitive impairment, no dementia (CIND) and 3.11 (1.64-5.93) for incident AD. Among people with SCD at baseline, the multivariable-adjusted OR of incident CIND was 0.55(0.32-0.96) for hyperlipidemia; the multivariable-adjusted OR of incident AD was 1.21 (1.14-1.30) for older age, 0.32 (0.12-0.88) for high education, 2.60 (1.11-6.08) for carrying APOEɛ4 allele, and 0.34 (0.13-0.86) for high social support, whereas the multivariable-adjusted OR of incident VaD was 6.30 (1.71-23.18) for obesity. CONCLUSION: SCD affects over 40% of rural-dwelling cognitively unimpaired older adults in China. SCD is associated with accelerated progression to CIND and AD. Older age, lack of school education, APOEɛ4 allele, and low social support are associated with an increased risk of progression from SCD to AD, whereas obesity is related to accelerated progression to VaD.

De novo mitochondrial genome sequencing of Cladonia subulata and phylogenetic analysis with other dissimilar species.

In this study, the complete mitochondrial genome of Cladonia subulata (L.) FH Wigg was sequenced and assembled and then compared with those of other Cladonia species. The mitogenome of Cladonia subulata, the type species of Cladonia, consisted of a circular DNA molecule of 58,895 bp 44 genes (15 protein-coding genes, 2 rRNA genes, and 27 tRNA genes). The base composition had shown an obvious AT preference, and all 27 tRNA genes formed a typical clover structure. Comparison with other 7 Cladonia species indicated that the duplication/loss of tRNAs had occurred during evolution, and introns appeared to explain the variation in cox1 genes in Cladonia, the mitochondrial genome tends to be generally conservative and local dynamic changes. Repeat sequences were mainly located in gene intervals, which were mainly distributed among intergenic spacers and may cause rearrangement of the mitogenome. The phylogenetic results showed that Cladonia subulata and C. polycarpoides were assigned to the Cladonia Subclade. The results add to the available mitochondrial genome sequence information of Cladonia subulata, provide basic data for the systematic development, resource protection, and genetic diversity research in Cladonia subulata, and also provide theoretical support for further genomic research of lichens.