The associations of serum isoleucine with Alzheimer`s disease on assisting diagnosis, predicting conversion and assessing cognition.

Background: Advances in blood biomarker discovery have enabled the improved diagnosis and prognosis of Alzheimer's disease (AD). Most branched-chain amino acids, except isoleucine (Ile), are correlated with both mild cognitive impairment (MCI) and AD. Therefore, this study investigated the association between serum Ile levels and MCI/AD. Methods: This study stratified 700 participants from the Alzheimer's Disease Neuroimaging Initiative database into four diagnostic groups: cognitively normal, stable MCI, progressive MCI, and AD. Analysis of covariance and chi-square analyses were used to test the demographic data. Receiver operating curve analyses were used to calculate the diagnostic accuracy of different biomarkers and were compared using MedCalc 20. Additionally, Cox proportional hazards models were used to measure the ability of serum Ile levels to predict disease conversion. Finally, a linear mixed-effects model was used to evaluate the associations between serum Ile levels and cognition, brain structure, and metabolism. Results: Serum Ile concentration was decreased in AD and demonstrated significant diagnostic efficacy. The combination of serum Ile and cerebrospinal fluid (CSF) phosphorylated tau (P-tau) levels improved the diagnostic accuracy in AD compared to T-tau alone. Serum Ile levels significantly predicted the conversion from MCI to AD (cutoff value = 78.3 µM). Finally, the results of this study also revealed a correlation between serum Ile levels and the Alzheimer's Disease Assessment Scale cognitive subscale Q4. Conclusions: Serum Ile level may be a potential biomarker of AD. Ile had independent diagnostic efficacy and significantly improved the diagnostic accuracy of CSF P-tau in AD. Patients with MCI with a lower serum Ile level had a higher risk of progression to AD and a worse cognition assessment.

Whole Genome Duplication Events Likely Contributed to the Aquatic Adaptive Evolution of Parkerioideae.

As the only aquatic lineage of Pteridaceae, Parkerioideae is distinct from many xeric-adapted species of the family and consists of the freshwater Ceratopteris species and the only mangrove ferns from the genus Acrostichum. Previous studies have shown that whole genome duplication (WGD) has occurred in Parkerioideae at least once and may have played a role in their adaptive evolution; however, more in-depth research regarding this is still required. In this study, comparative and evolutionary transcriptomics analyses were carried out to identify WGDs and explore their roles in the environmental adaptation of Parkerioideae. Three putative WGD events were identified within Parkerioideae, two of which were specific to Ceratopteris and Acrostichum, respectively. The functional enrichment analysis indicated that the lineage-specific WGD events have played a role in the adaptation of Parkerioideae to the low oxygen concentrations of aquatic habitats, as well as different aquatic environments of Ceratopteris and Acrostichum, such as the adaptation of Ceratopteris to reduced light levels and the adaptation of Acrostichum to high salinity. Positive selection analysis further provided evidence that the putative WGD events may have facilitated the adaptation of Parkerioideae to changes in habitat. Moreover, the gene family analysis indicated that the plasma membrane H+-ATPase (AHA), vacuolar H+-ATPase (VHA), and suppressor of K+ transport growth defect 1 (SKD1) may have been involved in the high salinity adaptation of Acrostichum. Our study provides new insights into the evolution and adaptations of Parkerioideae in different aquatic environments.

Olefin skeletal rearrangement enabling access to multiarylated N-sulfonyl amidines.

A base-promoted olefin skeletal rearrangement strategy from para-quinone methides (p-QMs) and N-fluoroarenesulfonamides is reported, enabling direct nitrogen insertion of olefins to produce a series of multiarylated (Z)-N-sulfonyl amidines with complete stereoselectivity and generally good yields. Using p-QMs without o-hydroxy substituents gave triarylated N-sulfonyl amidines, whereas tetraarylated N,N'-disulfonyl amidines were synthesized with the existence of o-hydroxy groups.

Which surgery is better for obese patients with lumbar degenerative diseases: open TLIF or Endo-LIF? A retrospective matched case-control study.

OBJECTIVE: This study aimed to evaluate short-term clinical efficacy of percutaneous endoscopic posterior lumbar interbody fusion (Endo-LIF) in the treatment of obese patients with lumbar degenerative diseases (LDD). METHODS: Patients who underwent single-level lumbar fusion surgery from July 2020 to July 2022 were retrospectively analyzed in this study. The main inclusion criterion was a body mass index (BMI) ≥30kg/m2. A matched case-control design was conducted to compare the short-term outcomes between the Endo-LIF and transforaminal lumbar interbody fusion (TLIF) in obese patients. Cases were defined as those who underwent Endo-LIF, and controls were matched from those patients with open TLIF according to corresponding matched criteria. Surgeon satisfaction was evaluated by questionnaires at the end of each surgery, patient satisfaction and their willingness to undergo the same surgery again were collected. RESULTS: Two groups of patients were successfully completed surgery. In comparison with the open TLIF group, the Endo-LIF group had significantly less blood loss, less time to postoperative ambulation, less postoperative complications and shorter hospitalization days, but longer operation time and x-ray exposure times. The satisfaction of surgeons and patients in Endo-LIF group significantly were superior to open TLIF group. CONCLUSION: Endo-LIF is a safe and effective surgery in the treatment of obese patients. Although this procedure needs longer operation time and x-ray exposure times, it still maybe a promising option for obese patients with LDD.

Insights into cryptic speciation of quillworts in China.

Cryptic species are commonly misidentified because of high morphological similarities to other species. One group of plants that may harbor large numbers of cryptic species is the quillworts (Isoëtes spp.), an ancient aquatic plant lineage. Although over 350 species of Isoëtes have been reported globally, only ten species have been recorded in China. The aim of this study is to better understand Isoëtes species diversity in China. For this purpose, we systematically explored the phylogeny and evolution of Isoëtes using complete chloroplast genome (plastome) data, spore morphology, chromosome number, genetic structure, and haplotypes of almost all Chinese Isoëtes populations. We identified three ploidy levels of Isoëtes in China-diploid (2n = 22), tetraploid (2n = 44), and hexaploid (2n = 66). We also found four megaspore and microspore ornamentation types in diploids, six in tetraploids, and three in hexaploids. Phylogenetic analyses confirmed that I. hypsophila as the ancestral group of the genus and revealed that Isoëtes diploids, tetraploids, and hexaploids do not form monophyletic clades. Most individual species possess a single genetic structure; however, several samples have conflicting positions on the phylogenetic tree based on SNPs and the tree based on plastome data. All 36 samples shared 22 haplotypes. Divergence time analysis showed that I. hypsophila diverged in the early Eocene (∼48.05 Ma), and most other Isoëtes species diverged 3-20 Ma. Additionally, different species of Isoëtes were found to inhabit different water systems and environments along the Yangtze River. These findings provide new insights into the relationships among Isoëtes species in China, where highly similar morphologic populations may harbor many cryptic species.

The RNA cargo in small extracellular vesicles from chicken eggs is bioactive in C57BL/6 J mice and human peripheral blood mononuclear cells ex vivo.

Small extracellular vesicles (sEVs) and their RNA cargo in milk are bioavailable in humans, pigs, and mice, and their dietary depletion and supplementation elicits phenotypes. Little is known about the content and biological activity of sEVs in foods of animal origin other than milk. Here we tested the hypothesis that sEVs in chicken eggs (Gallus gallus) facilitate the transfer of RNA cargo from an avian species to humans and mice, and their dietary depletion elicits phenotypes. sEVs were purified from raw egg yolk by ultracentrifugation and authenticated by transmission electron microscopy, nano-tracking device, and immunoblots. The miRNA profile was assessed by RNA-sequencing. Bioavailability of these miRNAs in humans was assessed by egg feeding study in adults, and by culturing human peripheral blood mononuclear cells (PBMCs) with fluorophore-labeled egg sEVs ex vivo. To further assess bioavailability, fluorophore-labeled miRNAs, encapsulated in egg sEVs, were administered to C57BL/6 J mice by oral gavage. Phenotypes of sEV RNA cargo depletion were assessed by feeding egg sEV and RNA-defined diets to mice and using spatial learning and memory in the Barnes and water mazes as experimental readouts. Egg yolk contained 6.30 × 1010 ± 6.06 × 109 sEVs/mL, which harbored eighty-three distinct miRNAs. Human PBMCs internalized sEVs and their RNA cargo. Egg sEVs, loaded with fluorophore-labeled RNA and administered orally to mice, accumulated primarily in brain, intestine and lungs. Spatial learning and memory (SLM) was compromised in mice fed on egg sEV- and RNA-depleted diet compared to controls. Egg consumption elicited an increase of miRNAs in human plasma. We conclude that egg sEVs and their RNA cargo probably are bioavailable. The human study is registered as a clinical trial and accessible at https://www.isrctn.com/ISRCTN77867213.

Azofuran activation for annulative rearrangement enabled by gold(I)/Brønsted acid relay catalysis.

A novel gold(I)/Brønsted acid relay catalysis enabling azofuran activation to induce annulative rearrangement from 3-yne-1,2-diols and aryldiazonium tetrafluoroborates is reported, producing a series of furan-2-yl-substituted pyrrol-2-ones bearing a quaternary carbon center with good yields. Exchanging aryldiazonium tetrafluoroborate for azofuran led to skeletally identical but substituent-diverse furan-2-yl-containing pyrrol-2-ones with good yields, supporting the key azofuran activation and annulative rearrangement by gold/Brønsted acid relay catalysis.

Gold self-relay catalysis enabling annulative oxygenation of propargylic alcohols with O-nucleophiles.

A new gold(I) self-relay catalysis reaction enabling the annulative oxygenation of propargylic alcohols with various O-nucleophiles, such as carboxylic acids, alcohols and TBHP, is reported, producing a series of functionalized benzofurans in moderate to good yields under mild conditions. This protocol benefits from the π- and σ-Lewis acid capability of gold complexes, demonstrating high molecular convergence, broad substrate flexibility, high functional group compatibility and mild conditions.

[Spatiotemporal Dynamic Evolution and Gravity Center Migration of Carbon Emissions in the Main Urban Area of Chongqing over the Past 20 Years].

Global warming caused by carbon emissions is an environmental issue that is of great concern to all walks of life. Dynamic monitoring of the spatiotemporal evolution of urban carbon emissions is an important part of achieving the regional double-carbon goals. Taking the main urban area of Chongqing as an example, based on the data of land use and energy consumption, this study estimated the carbon emissions of 153 townships and streets in the main urban area of Chongqing from 2000 to 2020 by using the carbon emission coefficient method. Additionally, using the ESTDA framework to pass the LISA time path, spatiotemporal transition, and the standard deviation ellipse model from the perspective of spatiotemporal interaction, the spatiotemporal dynamic evolution of carbon emissions in the main urban area and the shift in the center of gravity over the past 20 years were analyzed. The results showed that: ① in the past 20 years, the carbon emissions in the main urban and rural areas have had a significant positive spatial correlation, and the spatial convergence showed a trend of first decreasing and then increasing. ② In the past 20 years, there were 126 township streets with low and medium relative lengths (accounting for 82%), indicating that the local spatial structure of township carbon emissions in the main urban area had strong stability; the total number of township streets with low and medium curvatures was 138 (accounting for 90%), indicating that the volatility of the main urban and rural carbon emissions in the direction of spatial dependence was relatively stable; there were 113 township streets (accounting for 74%) of the synergistic growth type, indicating that the main urban and rural carbon emissions were relatively stable. The emission pattern had strong spatial integration. ③ In the past 20 years, the spatiotemporal agglomeration index was greater than 70%, indicating that the local spatial correlation pattern and agglomeration characteristics of carbon emissions in the main urban and rural areas had strong stability. 4 In the past 20 years, the center of carbon emission in the main urban area had been distributed between 106°30'43″-106°32'42″E, 29°33'34″-29°35'56″N, and the center of gravity shifted to the northeast as a whole. The spatial distribution changed from the "northwest-southeast" pattern to the "northeast-southwest" pattern. These results can provide reference for the green and low-carbon sustainable development of Chongqing and the formulation of differentiated emission reduction policies, as well as provide reference for other similar mountain cities in western China.

Synthesis, Characterization of Low Molecular Weight Chitosan Selenium Nanoparticles and Its Effect on DSS-Induced Ulcerative Colitis in Mice.

Selenium nanoparticles have attracted extensive attention due to their good bioavailability and activity. In the present study, a new form of selenium nanoparticle (Low molecular weight chitosan selenium nanoparticles (LCS-SeNPs)) were synthesized in a system of sodium selenite and acetic acid. The size, element state, morphology and elementary composition of LCS-SeNPs were characterized by using various spectroscopic and microscopic measurements. The protection of LCS-SeNPs against dextran sulfate sodium (DSS)-induced intestinal barrier dysfunction and the inherent mechanisms of this process were investigated. The results showed that LCS-SeNPs, with an average diameter of 198 nm, zero-valent and orange-red relatively uniform spherical particles were prepared. LCS-SeNPs were mainly composed of C, N, O and Se elements, of which Se accounted for 39.03% of the four elements C, N, O and Se. LCS-SeNPs reduced colon injury and inflammation symptoms and improved intestinal barrier dysfunction. LCS-SeNPs significantly reduced serum and colonic inflammatory cytokines TNF-α and IL-6 levels. Moreover, LCS-SeNPs remarkably increased antioxidant enzyme GSH-Px levels in serum and colonic tissue. Further studies on inflammatory pathways showed that LCS-SeNPs alleviated DSS-induced colitis through the NF-κB signaling pathway, and relieved inflammatory associated oxidative stress through the Nrf2 signaling pathway. Our findings suggested that LCS-SeNPs are a promising selenium species with potential applications in the treatment of oxidative stress related inflammatory intestinal diseases.

Untying the Gordian knot of plastid phylogenomic conflict: A case from ferns.

Phylogenomic studies based on plastid genome have resolved recalcitrant relationships among various plants, yet the phylogeny of Dennstaedtiaceae at the level of family and genera remains unresolved due to conflicting plastid genes, limited molecular data and incomplete taxon sampling of previous studies. The present study generated 30 new plastid genomes of Dennstaedtiaceae (9 genera, 29 species), which were combined with 42 publicly available plastid genomes (including 24 families, 27 genera, 42 species) to explore the evolution of Dennstaedtiaceae. In order to minimize the impact of systematic errors on the resolution of phylogenetic inference, we applied six strategies to generate 30 datasets based on CDS, intergenic spacers, and whole plastome, and two tree inference methods (maximum-likelihood, ML; and multispecies coalescent, MSC) to comprehensively analyze the plastome-scale data. Besides, the phylogenetic signal among all loci was quantified for controversial nodes using ML framework, and different topologies hypotheses among all datasets were tested. The species trees based on different datasets and methods revealed obvious conflicts at the base of the polypody ferns. The topology of the "CDS-codon-align-rm3" (CDS with the removal of the third codon) matrix was selected as the primary reference or summary tree. The final phylogenetic tree supported Dennstaedtiaceae as the sister group to eupolypods, and Dennstaedtioideae was divided into four clades with full support. This robust reconstructed phylogenetic backbone establishes a framework for future studies on Dennstaedtiaceae classification, evolution and diversification. The present study suggests considering plastid phylogenomic conflict when using plastid genomes. From our results, reducing saturated genes or sites can effectively mitigate tree conflicts for distantly related taxa. Moreover, phylogenetic trees based on amino acid sequences can be used as a comparison to verify the confidence of nucleotide-based trees.

The complete chloroplast genome sequence of the water fern Ceratopteris thalictroides (Pteridaceae).

This work determined and analyzed the complete chloroplast genome sequence of Ceratopteris thalictroides (Linnaeus) Brongniart 1822 (Pteridaceae). The results indicate that the total chloroplast genome size of C. thalictroides is 149,399 bp in length, and the genome contains a large single-copy (LSC) region of 83,580 bp, a small single-copy (SSC) region of 21,241 bp, and a pair of inverted repeat (IR) regions of 22,289 bp. The GC content of C. thalictroides is 36.7%. The genome encodes a total of 131 unique genes, including 82 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. The phylogenetic analysis results strongly suggest that C. thalictroides is closely related to C. cornuta.

Regio- and Enantioselective Synthesis of Dihydropyrido[1,2-a]indoles via Catalytic Asymmetric Annulative Allylic Alkylation.

A palladium-catalyzed asymmetric annulative allylic alkylation reaction of 2-[(1H-indol-2-yl)methyl]malonates with (E)-but-2-ene-1,4-diyl dicarbonates is described, leading to the regio- and enantioselective synthesis of dihydropyrido[1,2-a]indoles with a chiral cyclic allyl stereocenter adjacent to the ring-junction nitrogen atom in moderate to good yields. The salient features of this protocol include mild conditions, a broad substrate scope, and good compatibility with substituents as well as high regio- and stereoselectivities, providing a catalytic asymmetric entry for fabricating chiral pyridoindole scaffolds.

Azoarene activation for Schmidt-type reaction and mechanistic insights.

The Schmidt rearrangement, a reaction that enables C-C or C-H σ bond cleavage and nitrogen insertion across an aldehyde or ketone substrate, is one of the most important and widely used synthetic tools for the installation of amides and nitriles. However, such a reaction frequently requires volatile, potentially explosive, and highly toxic azide reagents as the nitrogen donor, thus limiting its application to some extent. Here, we show a Schmidt-type reaction where aryldiazonium salts act as the nitrogen precursor and in-situ-generated cyclopenta-1,4-dien-1-yl acetates serve as pronucleophiles from gold-catalyzed Nazarov cyclization of 1,3-enyne acetates. Noteworthy is that cycloketone-derived 1,3-enyne acetates enabled ring-expansion relay to access a series of 2-pyridone-containing fused heterocycles, in which nonsymmetric cycloketone-derived counterparts demonstrated high regioselectivity. Aside from investigating the scope of this Schmidt-type reaction, mechanistic details of this transformation are provided by performing systematic theoretical calculations.

Electrochemical selective annulative amino-ketalization and amino-oxygenation of 1,6-enynes.

A new electrochemical selective annulative amino-ketalization and amino-oxygenation of 1,6-enynes with disulfonimides and alcohols is reported, producing a series of functionalized benzofurans under catalyst- and oxidant-free conditions. The annulative aminoketalization proceeds with simple short-chain alcohols such as methanol, ethanol and n-propanol as O-nucleophilic reagents, while the reaction occurs in the annulative aminooxygenation direction in the presence of water and large steric sec-butyl alcohol (SBA).

Phylogenomic Analysis Reconstructed the Order Matoniales from Paleopolyploidy Veil.

Phylogenetic conflicts limit our understanding of the evolution of terrestrial life under multiple whole genome duplication events, and the phylogeny of early terrestrial plants remains full of controversy. Although much incongruence has been solved with so-called robust topology based on single or lower copy genes, the evolutionary mechanisms behind phylogenetic conflicts such as polyploidization remain poorly understood. Here, through decreasing the effects of polyploidization and increasing the samples of species, which represent all four orders and eight families that comprise early leptosporangiate ferns, we have reconstructed a robust phylogenetic tree and network with 1125 1-to-1 orthologs based on both coalescent and concatenation methods. Our data consistently suggest that Matoniales, as a monophyletic lineage including Matoniaceae and Dipteridaceae, should be redefined as an ordinal rank. Furthermore, we have identified and located at least 11 whole-genome duplication events within the evolutionary history of four leptosporangiates lineages, and associated polyploidization with higher speciation rates and mass extinction events. We hypothesize that paleopolyploidization may have enabled leptosporangiate ferns to survive during mass extinction events at the end Permian period and then flourish throughout the Mesozoic era, which is supported by extensive fossil records. Our results highlight how ancient polyploidy can result in rapid species radiation, thus causing phylogenetic conflicts yet allowing plants to survive and thrive during mass extinction events.

Lycophyte transcriptomes reveal two whole-genome duplications in Lycopodiaceae: Insights into the polyploidization of Phlegmariurus.

Lycophytes are an ancient clade of the non-flowering vascular plants with chromosome numbers that vary from tens to hundreds. They are an excellent study system for examining whole-genome duplications (WGDs), or polyploidization, in spore-dispersed vascular plants. However, a lack of genome sequence data limits the reliable detection of very ancient WGDs, small-scale duplications (SSDs), and recent WGDs. Here, we integrated phylogenomic analysis and the distribution of synonymous substitutions per synonymous sites (Ks) of the transcriptomes of 13 species of lycophytes to identify, locate, and date multiple WGDs in the lycophyte family Lycopodiaceae. Additionally, we examined the genus Phlegmariurus for signs of genetic discordance, which can provide valuable insight into the underlying causes of such conflict (e.g., hybridization, incomplete lineage sorting, or horizontal gene transfer).We found strong evidence that two WGD events occurred along the phylogenetic backbone of Lycopodiaceae, with one occurring in the common ancestor of extant Phlegmariurus (Lycopodiaceae) approximately 22-23 million years ago (Mya) and the other occurring in the common ancestor of Lycopodiaceae around 206-214 Mya. Interestingly, we found significant genetic discordance in the genus Phlegmariurus, indicating that the genus has a complex evolutionary history. This study provides molecular evidence for multiple WGDs in Lycopodiaceae and offers phylogenetic clues to the evolutionary history of Lycopodiaceae.

The associations of serum valine with mild cognitive impairment and Alzheimer's disease.

BACKGROUND: The introduction of metabolomics makes it possible to study the characteristic changes of peripheral metabolism in Alzheimer's disease (AD). Recent studies have found that the levels of valine are related to mild cognitive impairment (MCI) and AD. AIMS: This study aimed to further clarify the characteristics of valine levels in MCI and AD. METHODS: A total of 786 participants from the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1) cohort were selected to evaluate the relationships between serum valine and cerebrospinal fluid (CSF) biomarkers, brain structure (magnetic resonance imaging, MRI), cerebral glucose metabolism (18F-fluorodeoxyglucose-positron emission tomography, FDG-PET), and cognitive declines, through different cognitive subgroups. RESULTS: Serum valine was decreased in patients with AD compared with cognitive normal (CN) and stable MCI (sMCI), and in progressive MCI (pMCI) compared with CN. Serum valine was negatively correlated with CSF total tau (t-tau) and phosphorylated tau (p-tau) in pMCI. Serum valine significantly predicted conversion from MCI to AD. In addition, serum valine was related to the rate of change of cerebral glucose metabolism during the follow-up period in pMCI. CONCLUSIONS: Serum valine may be a peripheral biomarker of pMCI and AD, and its level predicts the progression of MCI to AD. Our study may help to reveal the metabolic changes during AD disease trajectory and its relationship to clinical phenotype.

Nitrative bicyclization of 1,7-diynes for accessing skeletally diverse tricyclic pyrroles.

A novel metal-free nitrative bicyclization of 1,7-diynes with tBuONO in the presence of H2O is reported, producing three types of skeletally diverse tricyclic pyrroles, namely pyrrolo[3,4-c]quinolines, chromeno[3,4-c]pyrroles and benzo[e]isoindoles, with moderate to good yields by simply tuning the linkers of the 1,7-diynes. This domino protocol demonstrates remarkable compatibility regarding 1,7-diynes with different linkers, such as nitrogen and oxygen atoms and a hydroxymethyl group, and tBuONO plays dual roles as a nitro precursor as well as a nitrogen atom source.

Complete mitochondrial genome of Dermanyssus gallinae (Arthropoda: Dermanyssidae) isolate from China.

The complete mitochondrial genome of Dermanyssus gallinae isolated from China is reported for the first time in this study. Its entire mitogenome is 16, 184 bp in length, contained 13 protein-coding genes, 2 ribosomal RNA genes, 21 transfer RNA genes, and 1 non-coding region. The phylogenetic analysis by maximum likelihood method show that D. gallinae isolated from China is in the same clade with the genus of Psoroptes. This is the first complete mitochondrial genome of D. gallinae.