The Possible Earliest Allopolyploidization in Tracheophytes Revealed by Phylotranscriptomics and Morphology of Selaginellaceae.

Selaginellaceae, originated in the Carboniferous and survived the Permian-Triassic mass extinction, is the largest family of lycophyte, which is sister to other tracheophytes. It stands out from tracheophytes by exhibiting extraordinary habitat diversity and lacking polyploidization. The organelle genome-based phylogenies confirmed the monophyly of Selaginella, with six or seven subgenera grouped into two superclades, but the phylogenetic positions of the enigmatic Selaginella sanguinolenta clade remained problematic. Here, we conducted a phylogenomic study on Selaginellaceae utilizing large-scale nuclear gene data from RNA-seq to elucidate the phylogeny and explore the causes of the phylogenetic incongruence of the S. sanguinolenta clade. Our phylogenetic analyses resolved three different positions of the S. sanguinolenta clade, which were supported by the sorted three nuclear gene sets, respectively. The results from the gene flow test, species network inference, and plastome-based phylogeny congruently suggested a probable hybrid origin of the S. sanguinolenta clade involving each common ancestor of the two superclades in Selaginellaceae. The hybrid hypothesis is corroborated by the evidence from rhizophore morphology and spore micromorphology. The chromosome observation and Ks distributions further suggested hybridization accompanied by polyploidization. Divergence time estimation based on independent datasets from nuclear gene sets and plastid genome data congruently inferred that allopolyploidization occurred in the Early Triassic. To our best knowledge, the allopolyploidization in the Mesozoic reported here represents the earliest record of tracheophytes. Our study revealed a unique triad of phylogenetic positions for a hybrid-originated group with comprehensive evidence and proposed a hypothesis for retaining both parental alleles through gene conversion.

The geriatric nutrition risk index is longitudinally associated with incident Sarcopenia: evidence from a 5-year prospective cohort.

BACKGROUND: Previous studies investigating the association between the geriatric nutrition risk index (GNRI) and sarcopenia either lacked longitudinal evidence or narrowly focused on specific populations. AIMS: We aimed to reveal longitudinal associations of GNRI with sarcopenia risk in community-dwelling Chinese. We also investigated interaction effects of potential factors on such associations. METHODS: We included participants aged ≥ 50 years with sufficient data from the WCHAT study who did not have sarcopenia at baseline and completed sarcopenia assessment during follow-up. GNRI was calculated according to the formula based on serum albumin, height and weight. Sarcopenia was diagnosed according to the 2019 AWGS consensus. Longitudinal associations between GNRI and sarcopenia were estimated by logistic regression with GNRI as either a continuous or categorical variable by tertiles, using generalized estimating equations (GEE) as sensitivity analyses. Subgroup analyses by potential covariates were conducted to detect interaction effects. RESULTS: A total of 1907 participants without baseline sarcopenia were finally included, of whom 327 (17.1%) developed incident sarcopenia during 5-year follow-up. After controlling for confounders, sarcopenia risk decreased with each one standard deviation increase in GNRI (ORadjusted=0.36, 95% CI 0.31-0.43), and it also decreased successively from the lowest (< 111.2) through middle (111.2-117.7) to the highest (≥ 117.8) tertile of the GNRI level (P for trend < 0.001). Similar results were yielded by GEE. Such associations generally remained robust across subgroups with distinct characteristics, while significant differences were observed between different age groups (≥ 65 vs. <65 years) (interaction P-value < 0.05). CONCLUSION: GNRI is longitudinally associated with sarcopenia risk with possibly age-specific differences in association magnitude, which holds implications for policymakers to conduct population-based risk assessment.

The evolution of extremely diverged plastomes in Selaginellaceae (lycophyte) is driven by repeat patterns and the underlying DNA maintenance machinery.

Two factors are proposed to account for the unusual features of organellar genomes: the disruptions of organelle-targeted DNA replication, repair, and recombination (DNA-RRR) systems in the nuclear genome and repetitive elements in organellar genomes. Little is known about how these factors affect organellar genome evolution. The deep-branching vascular plant family Selaginellaceae is known to have a deficient DNA-RRR system and convergently evolved organellar genomes. However, we found that the plastid genome (plastome) of Selaginella sinensis has extremely accelerated substitution rates, a low GC content, pervasive repeat elements, a dynamic network structure, and it lacks direct or inverted repeats. Unexpectedly, its organelle DNA-RRR system is short of a plastid-targeted Recombinase A1 (RecA1) and a mitochondrion-targeted RecA3, in line with other explored Selaginella species. The plastome contains a large collection of short- and medium-sized repeats. Given the absence of RecA1 surveillance, we propose that these repeats trigger illegitimate recombination, accelerated mutation rates, and structural instability. The correlations between repeat quantity and architectural complexity in the Selaginella plastomes support these conclusions. We, therefore, hypothesize that the interplay of the deficient DNA-RRR system and the high repeat content has led to the extraordinary divergence of the S. sinensis plastome. Our study not only sheds new light on the mechanism of plastome divergence by emphasizing the power of cytonuclear integration, but it also reconciles the longstanding contradiction on the effects of DNA-RRR system disruption on genome structure evolution.

The first homosporous lycophyte genome revealed the association between the recent dynamic accumulation of LTR-RTs and genome size variation.

The contrasting genome size between homosporous and heterosporous plants is fascinating. Different from the heterosporous seed plants and mainly homosporous ferns, the lycophytes are either heterosporous (Isoetales and Selaginellales) or homosporous (Lycopodiales). Many lycophytes are the resource plants of Huperzine A (HupA) which is invaluable for treating Alzheimer's disease. For the seed-free vascular plants, several high-quality genomes of heterosporous Selaginella, homosporous ferns (maidenhair fern, monkey spider tree fern), and heterosporous ferns (Azolla) have been published and provided important insights into the origin and evolution of early land plants. However, the homosporous lycophyte genome has not been decoded. Here, we assembled the first homosporous lycophyte genome and conducted comparative genomic analyses by applying a reformed pipeline for filtering out non-plant sequences. The obtained genome size of Lycopodium clavatum is 2.30 Gb, distinguished in more than 85% repetitive elements of which 62% is long terminal repeat (LTR). This study disclosed a high birth rate and a low death rate of the LTR-RTs in homosporous lycophytes, but the opposite occurs in heterosporous lycophytes. we propose that the recent activity of LTR-RT is responsible for the immense genome size variation between homosporous and heterosporous lycophytes. By combing Ks analysis with a phylogenetic approach, we discovered two whole genome duplications (WGD). Morover, we identified all the five recognized key enzymes for the HupA biosynthetic pathway in the L. clavatum genome, but found this pathway incomplete in other major lineages of land plants. Overall, this study is of great importance for the medicinal utilization of lycophytes and the decoded genome data will be a key cornerstone to elucidate the evolution and biology of early vascular land plants.

Mitogenome-based phylogenomics provides insights into the positions of the enigmatic sinensis group and the sanguinolenta group in Selaginellaceae (Lycophyte).

Spikemoss (Selaginellaceae) is one of the basal lineages of vascular plants. This family has a single genus Selaginella which consists of about 750 extant species. The phylogeny of Selaginellaceae has been extensively studied mainly based on plastid DNA and a few nuclear sequences. However, the placement of the enigmatic sinensis group is a long-term controversy because of the long branch in the plastid DNA phylogeny. The sanguinolenta group is also a phylogenetically problematic clade owing to two alternative positions resulted from different datasets. Here, we newly sequenced 34 mitochondrial genomes (mitogenomes) of individuals representing all seven subgenera and major clades in Selaginellaceae. We assembled the draft mitogenomes and annotated the genes and performed phylogenetic analyses based on the shared 17 mitochondrial genes. Our major results include: (1) all the assembled mitogenomes have complicated structures, unparalleled high GC content and a small gene content set, and the positive correlations among GC content, substitution rates and the number of RNA editing sites hold; (2) the sinensis group was well supported as a member of subg. Stachygynandrum; (3) the sanguinolenta group was strongly resolved as sister to all other Selaginella species except for subg. Selaginella. This study demonstrates the potential of mitogenome data in providing novel insights into phylogenetically recalcitrant problems.

Plastid phylogenomic analyses of the Selaginella sanguinolenta group (Selaginellaceae) reveal conflict signatures resulting from sequence types, outlier genes, and pervasive RNA editing.

Different from the generally conserved plastomes (plastid genomes) of most land plants, the Selaginellaceae plastomes exhibit dynamic structure, high GC content and high substitution rates. Previous plastome analyses identified strong conflict on several clades in Selaginella, however the factors causing the conflictions and the impact on the phylogenetic inference have not been sufficiently investigated. Here, we dissect the distribution of phylogenetic signals and conflicts in Selaginella sanguinolenta group, the plastome of which is DR (direct repeats) structure and with genome-wide RNA editing. We analyzed the data sets including 22 plastomes representing all species of the S. sanguinolenta group, covering the entire geographical distribution from the Himalayas to Siberia and the Russian Far East regions. We recovered four different topologies by applying multispecies coalescent (ASTRAL) and concatenation methods (IQ-TREE and RAxML) on four data sets of PC (protein-coding genes), NC (non-coding sequences), PCN (the concatenated PC and NC), and RC (predicted RNA editing sites "C" were corrected by "T"), respectively. Six monophyletic clades, S. nummularifolia clade, S. rossii clade, S. sajanensis clade, S. sanguinolenta I clade, S. sanguinolenta II clade, and S. sanguinolenta III clade, were consistently resolved and supported by the characteristics of GC content, RNA editing frequency, and gene content. However, the relationships among these clades varied across the four topologies. To explore the underlying causes of the uncertainty, we compared the phylogenetic signals of the four topologies. We identified that the sequence types (coding versus non-coding), outlier genes (genes with extremely high |ΔGLS| values), and C-to-U RNA editing frequency in the protein-coding genes were responsible for the unstable phylogenomic relationship. We further revealed a significant positive correlation between the |ΔGLS| values and the variation coefficient of the RNA editing number. Our results demonstrated that the coalescent method performed better than the concatenation method in overcoming the problems caused by outlier genes and extreme RNA editing events. Our study particularly focused on the importance of exploring the plastid phylogenomic conflicts and suggested conducting concatenated analyses cautiously when adopting organelle genome data.

Associations of geriatric nutrition risk index and other nutritional risk-related indexes with sarcopenia presence and their value in sarcopenia diagnosis.

OBJECTIVE: Standard modalities recommended for sarcopenia diagnosis may be unavailable in primary care settings. We aimed to comprehensively evaluate and compare associations of some better popularized nutritional risk-related indexes with sarcopenia presence and their value in sarcopenia diagnosis in community-dwelling middle-aged and elderly adults, including geriatric nutrition risk index (GNRI), albumin (ALB), calf circumference (CC), mid-arm circumference (MAC), triceps skinfold thickness (TST) and body mass index (BMI). METHODS: Based on the West China Health and Aging Trend study, the current study included participants aged 50 or older who were recruited in 2018. Sarcopenia-related assessment and diagnosis were in line with Asian Working Group for Sarcopenia 2019. For each single index, we assessed its association with sarcopenia presence by univariate and multivariate logistic regression analysis; we also computed diagnostic measures including the area under the receiver operating characteristic curve (AUC) and sensitivity, specificity, accuracy at the optimal cut-off value determined according to Youden's index. RESULTS: A total of 3829 subjects were included, consisting of 516 and 3313 subjects in the sarcopenia and non-sarcopenia groups, respectively. Regarding the risk for sarcopenia presence, the fully adjusted odds ratios of GNRI, ALB, CC, MAC, TST and BMI per standard deviation decrease were 2.95 (95% CI 2.51-3.47, P < 0.001), 1.01 (95% CI 0.90-1.15, P = 0.816), 4.56 (95% CI 3.82-5.44, P < 0.001), 4.24 (95% CI 3.56-5.05, P < 0.001), 1.67 (95% CI 1.92-1.45, P < 0.001) and 4.09 (95% CI 3.41-4.91, P < 0.001), respectively. Regarding the value in sarcopenia diagnosis in the entire study population, their AUCs could be ordered as MAC (0.85, 95% CI 0.83-0.86) > GNRI (0.80, 95% CI 0.78-0.82), CC (0.83, 95% CI 0.81-0.85), BMI (0.81, 95% CI 0.79-0.83) > TST (0.72, 95% CI 0.70-0.74) > ALB (0.62, 95% CI 0.60-0.65). At the relevant optimal cut-off values, the sensitivity was the highest for CC (0.83, 95% CI 0.80-0.87) and MAC (0.80, 95% CI 0.77-0.84), while GNRI showed the highest specificity (0.79, 95% CI 0.78-0.81) and accuracy (0.78, 95% 0.76-0.79). CONCLUSION: Overall diagnostic performance was the best for MAC, followed by GNRI, CC, BMI, and the worst for TST, ALB in distinguishing sarcopenia from non-sarcopenia in middle-aged and elderly adults in community-based settings. CC or MAC might do better in reducing missed diagnosis, while GNRI was superior in reducing misdiagnosis.

Distinctive evolutionary pattern of organelle genomes linked to the nuclear genome in Selaginellaceae.

Plastids and mitochondria are endosymbiotic organelles that store genetic information. The genomes of these organelles generally exhibit contrasting patterns regarding genome architecture and genetic content. However, they have similar genetic features in Selaginellaceae, and little is known about what causes parallel evolution. Here, we document the multipartite plastid genomes (plastomes) and the highly divergent mitochondrial genomes (mitogenomes) from spikemoss obtained by combining short- and long-reads. The 188-kb multipartite plastome has three ribosomal operon copies in the master genomic conformation, creating the alternative subgenomic conformation composed of 110- and 78-kb subgenomes. The long-read data indicated that the two different genomic conformations were present in almost equal proportions in the plastomes of Selaginella nipponica. The mitogenome of S. nipponica was assembled into 27 contigs with a total size of 110 kb. All contigs contained directly arranged repeats at both ends, which introduced multiple conformations. Our results showed that plastomes and mitogenomes share high tRNA losses, GC-biased nucleotides, elevated substitution rates and complicated organization. The exploration of nuclear-encoded organelle DNA replication, recombination and repair proteins indicated that, several single-targeted proteins, particularly plastid-targeted recombinase A1, have been lost in Selaginellaceae; conversely, the dual-targeted proteins remain intact. According to the reported function of recombinase A1, we propose that the plastomes of spikemoss often fail to pair homologous sequences during recombination, and the dual-targeted proteins play a key role in the convergent genetic features of plastomes and mitogenomes. Our results provide a distinctive evolutionary pattern of the organelle genomes in Selaginellaceae and evidence of their convergent evolution.

Ellipinema and ×Ellipisorus? Just Lepisorus (Polypodiaceae)!

The establishment of a segregate lepisoroid fern genus Ellipinema was mainly to accommodate the isolated position of Lepisorus jakonensis (Polypodiaceae) recovered in plastid gene tree. Using newly obtained nuclear data, we recovered that Ellipinema and allied genera, such as Lepidomicrosorium, Lemmaphyllum, Neolepisorus, Paragramma, Tricholepidium and Weatherbya are deeply nested within Lepisorus. The nuclear phylogeny showing incongruent phylogenetic placement in comparison with plastid results perhaps indicated ancient hybridization events. The diagnostic morphology characterizing Ellipinema - elliptic scale-like paraphyses, which is shared by all the taxa of sect. Lepisorus and sect. Hymenophyton - falls within the range of continuous variation in the type species Ellipinema jakonense (=Lepisorus jakonensis). Our study, which integrated molecular and morphological data, demonstrates that the segregation of Ellipinema and ×Ellipisorus (= ×Lepinema Li Bing Zhang & Liang Zhang, nom. illeg.) from Lepisorus should be rejected.

Protective effect of against ethanol-induced gastric ulcer and its mechanism.

: To investigate the protective effect of (FD) against ethanol-induced gastric ulcer and its mechanism. : Human gastric epithelial GES-1 cells were divided into normal control group, model control group, FD 95% alcohol extract group, FD 50% alcohol extract group and FD decoction extract group. Gastric ulcer was induced by treatment with 1% ethanol in GES-1 cells. The cell proliferation was detected with MTT method in each group. Sixty SD rats were randomly divided into normal control group, model control group, ranitidine group and low-dose, medium-dose, high-dose FD 95% alcohol extract groups (150, 300, 600 mg/kg). The corresponding drugs were administrated by gavage for The gastric ulcer model was induced by intragastric administration of anhydrous ethanol. The gastric ulcer area and ulcer inhibition rate of rats were measured in each group; the degree of gastricmucosal damage was observed by scanning electron microscopy; the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1ß in serum and the content of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), catalase (CAT) in gastric tissues were detected by ELISA method. : 95% alcohol extract of FD had the strongest protective effect on proliferation of GES-1 cells. In animal experiments, compared with the normal control group, a large area of ulcers appeared on the gastric mucosa in the model control group, while the ulcer areas of the FD groups and ranitidine group were significantly smaller than that of the model control group (all <0.05). Compared with the model control group, FD groups and ranitidine group significantly reduced the levels of TNF-α, IL-1ß, IL-6 in serum and the MDA content in the gastric tissues, and increased the activity of SOD, CAT and GSH in gastric tissues (all <0.05). : The 95% alcohol extract of FD can reduce the levels of TNF-α, IL-1ß and IL-6 in serum and the content of MDA in gastric tissues, and increase the activity of SOD, CAT and GSH in gastric tissues to achieve the protective effect against gastric ulcer.

Plastome-based phylogenomics resolves the placement of the sanguinolenta group in the spikemoss of lycophyte (Selaginellaceae).

Selaginellaceae have been shown to be monophyletic in previous studies, and include only the single genus Selaginella. However, the two most recent classifications of the genus disagree in terms of the number of subgenera recognized, and the position of problematic clades such as the "sanguinolenta" group, which has been resolved in quite different positions in different studies. Here, we performed a plastid-genome based phylogenomic analysis of Selaginellaceae to address this problem. The sanguinolenta group, represented here by three species, was resolved as sister to the remaining members of subg. Stachygynandrum. Additionally, subg. Exaltatae, subg. Ericetorum, and subg. Gymnogynum in clade A clustered into a well supported monophyletic clade but with conflicting topology between subgenera inside, which is possibly attributed to the early divergence among them. We uncovered substantial variation in both synonymous (dS) and nonsynonymous (dN) substitution rate, and GC content in plastomes of Selaginellaceae. The values of dS, dN, and GC content were significantly higher than those of other lycophytes (Isoetaceae and Lycopodiaceae). We observed a significant positive correlation between the high GC content, and the elevated dS and dN rates. In addition, the dS and dN values inferred among branches of Selaginellaceae were extremely variable. Our data indicate that this unevenly distributed substitution rate likely reflected relaxed or intensified selection among different lineages, which is possibly related to the inconsistency of the subgeneric phylogenetic topologies of Selaginellaceae.

Backbone phylogeny of Lepisorus (Polypodiaceae) and a novel infrageneric classification based on the total evidence from plastid and morphological data.

The fern genus Lepisorus represents one of the most complicated and controversial lineages in Polypodiaceae, with about 80 species which have been classified into several separate genera, and is notorious for its taxonomic difficulty. Despite progress in recent phylogenetic studies of the family Polypodiaceae involving Lepisorus and its allies, the deep phylogenetic relationship within this group of ferns is still unresolved, and no formal infrageneric classification has been proposed. This contribution presents the most comprehensive phylogenetic analysis of the genus, with 72% species sampled, using a total-evidence approach based on eight plastid markers and ≤25 morphological characters for each species. The analyses resolve the backbone relationship and yield the most robust phylogenetic framework to date. Congruent with previous studies but with new findings, the results herein show that Lepisorus is monophyletic when Neolepisorus, Lemmaphyllum, Tricholepidium, Neocheiropteris and Lepidomicrosorium are included, as well as Lepisorus jakonensis and Paragramma. Furthermore, 17 well-resolved clades are found in the phylogenetic topology, which can be characterized by morphological synapomorphies from traits of rhizome scales, laminae, sori and paraphyses. Based on molecular and morphological evidence, a new infrageneric classification system of Lepisorus is proposed which subdivided Lepisorus into 17 sections.

Correction to: Directed Repeats Co-occur with Few Short-Dispersed Repeats in Plastid Genome of a Spikemoss, Selaginella vardei (Selaginellaceae, Lycopodiopsida).

Following the publication of this article [1], the authors reported that the Fig. 2 described in the article had a mistake that two grey blocks in S. moellendorffii was not placed as background color, and in the Fig. 2 legend, chlL-chlN was wrongly written into chlL-chlL. They have therefore provided the following alternative Fig. 2 in this Correction article in order to show the accurate information.

Directed Repeats Co-occur with Few Short-Dispersed Repeats in Plastid Genome of a Spikemoss, Selaginella vardei (Selaginellaceae, Lycopodiopsida).

BACKGROUND: It is hypothesized that the highly conserved inverted repeats (IR) structure of land plant plastid genomes (plastomes) is beneficial for stabilizing plastome organization, whereas the mechanism of the occurrence and stability maintenance of the recently reported direct repeats (DR) structure is yet awaiting further exploration. Here we describe the DR structure of the Selaginella vardei (Selaginellaceae) plastome, to elucidate the mechanism of DR occurrence and stability maintenance. RESULTS: The plastome of S. vardei is 121,254 bp in length and encodes 76 genes, of which 62 encode proteins, 10 encode tRNAs, and four encode rRNAs. Unexpectedly, the two identical rRNA gene regions (13,893 bp) are arranged in a direct orientation (DR), rather than inverted. Comparing to the IR organization in Isoetes flaccida (Isoetaceae, Lycopodiopsida) plastome, a ca. 50-kb trnN-trnF inversion that spans one DR copy was found in the plastome of S. vardei, which might cause the orientation change. In addition, we find extremely rare short dispersed repeats (SDRs) in the plastomes of S. vardei and its closely related species S. indica. CONCLUSIONS: We suggest that the ca. 50-kb inversion resulted in the DR structure, and the reduction in SDRs plays a key role in maintaining the stability of plastomes with DR structure by avoiding potential secondary recombination. We further confirmed the presence of homologous recombination between DR regions, which are able to generate subgenomes and form diverse multimers. Our study deepens the understanding of Selaginella plastomes and provides new insights into the diverse plastome structures in land plants.

Phylogenetic relationships, possible ancient hybridization, and biogeographic history of Abies (Pinaceae) based on data from nuclear, plastid, and mitochondrial genomes.

Abies, the second largest genus of Pinaceae, consists of approximately 48 species occurring in the north temperate region. Previous molecular phylogenetic studies improved our understanding of relationships within the genus, but were limited by relying on only DNA sequence data from single genome and low taxonomic sampling. Here we use DNA data from three genomes (sequences of internal transcribed spacer of nrITS, three chloroplast DNA intergenic spacers, and two mitochondrial intergenic spacers) from 42 species to elucidate species relationships and construct the biogeographic history of Abies. We further estimated the divergence times of intercontinental disjunction using a relaxed molecular clock calibrated with three macro-fossils. Our phylogenetic analyses recovered six robust clades largely consistent with previous classifications of sections. A sister relationship between the eastern Asian and Europe-Mediterranean clades was highly supported. The monophyly of section Balsamea, disjunct in Far East and western North America, is supported by the nrITS data but not by the cpDNA data. Discordance on placement of section Balsamea between the paternally inherited cpDNA and maternally inherited mtDNA trees was also observed. The data suggested that ancient hybridization was likely involved in the origin of sect. Balsamea. Results from biogeographic analyses and divergence time estimation suggested an origin and early diversification of Abies in an area of high latitude around the Pacific during the Eocene. The present disjunction in eastern Asia and Europe-Mediterranean area of Abies was likely the result of southward migration and isolation by the Turgai Strait in the Late Eocene. An 'out-of-America' migration, for the origin of an eastern Asian and western North American disjunct species pairs in section Amabilis was supported. The results suggested a western North American origin of the section with subsequent dispersal across the Bering Land Bridge (BLB) to Japan during the Middle Miocene.

Identification of nicotinamide N-methyltransferase as a promising therapeutic target for sarcopenia.

Sarcopenia is a significant geriatric syndrome that involves the loss of skeletal muscle mass and strength. Due to its substantial endocrine role, the metabolic microenvironment of skeletal muscle undergoes changes with age. Examining the pathogenesis of sarcopenia through focusing on metabolic dysregulation could offer insights for developing more effective intervention strategies. In this study, we analyzed the transcriptomics data to identify specific genes involved in the regulation of metabolism in skeletal muscle during the development of sarcopenia. Three machine learning algorithms were employed to screen key target genes exhibiting strong correlations with metabolism, which were further validated using RNA-sequencing data and publicly accessible datasets. Among them, the metabolic enzyme nicotinamide N-methyltransferase (NNMT) was elevated in sarcopenia, and predicted sarcopenia with an area under the curve exceeding 0.7, suggesting it as a potential therapeutic target for sarcopenia. As expected, inhibition of NNMT improved the grip strength in aging mice and alleviated age-related decline in the mass index of the quadriceps femoris muscles and whole-body lean mass index. Additionally, the NNMTi treatment increased the levels of nicotinamide adenine dinucleotide (NAD+) content, as well as PGC1α and p-AMPK expression in the muscles of both the D-galactose-treated mouse model and naturally aging mouse model. Overall, this work demonstrates NNMT as a promising target for preventing age-related decline in muscle mass and strength.

Longitudinal associations between social support and sarcopenia: findings from a 5-year cohort study in Chinese aged ≥50 years.

OBJECTIVES: We aimed to investigate longitudinal associations of overall social support and its sub-domains with risk of sarcopenia and its related traits in community-dwelling Chinese aged ≥ 50 years. We also explored interaction effects of potential factors on such associations. DESIGN: A prospective cohort study. SETTING: Community-based setting in western China. PARTICIPANTS: We included participants aged ≥50 years with complete information necessary for analysis from the WCHAT study who did not have sarcopenia at baseline (2018) and had sufficient data for sarcopenia assessment during 2021-2023. MEASUREMENTS: Exposures included overall social support, subjective support, objective support and support utilization, which were assessed with the Social Support Rating Scale. Outcomes included sarcopenia, low muscle mass (LMM), low muscle strength and low physical performance, which were diagnosed with the 2019 AWGS consensus. Longitudinal associations between the exposures and outcomes were estimated by logistic regression, with generalized estimating equations (GEE) as sensitivity analyses. Subgroup analyses by potential covariates were conducted to detect interaction effects. RESULTS: A total of 1905 participants were finally included in the analytic sample, of whom 326 (17.1%) developed incident sarcopenia during 5-year follow-up. After controlling for confounders, higher degree of overall social support (OR = 0.87, 95%CI 0.76-0.99), subjective support (OR = 0.88, 95%CI 0.77-0.99) and support utilization (OR = 0.87, 95%CI 0.77-0.99) correlated with lower sarcopenia risk, among which higher support utilization degree was indicative of lower risk for LMM (OR = 0.88, 95%CI 0.79-0.98). GEE further revealed that overall support degree was negatively associated with risk for sarcopenia (OR = 0.86, 95%CI 0.76-0.98) and LMM (OR = 0.87, 95%CI 0.77-0.99). Objective support was neither significantly associated with sarcopenia nor its traits. No significant interaction effect was observed between overall support and the concerned confounders on sarcopenia (interaction P-value > 0.05). CONCLUSION: Overall social support degree was negatively associated with sarcopenia risk, possibly primarily through affecting muscle mass rather than muscle strength or physical performance, and such an association remained robust across subgroups with distinct characteristics. This holds implications for policymakers to conduct population-based risk assessment, and supportive strategies against sarcopenia should focus on enhancing subjective support and support utilization rather than objective support alone.

Exploring the impact of interleukins on sarcopenia development: A systematic review and meta-analysis.

BACKGROUND: The role of interleukins in sarcopenia development has been acknowledged, yet the specifics of their involvement remain to be fully understood. This study aimed to explore alterations in interleukin levels among sarcopenia patients. METHODS: Searches were conducted in Embase, Medline, and the Cochrane Library for literature published up to May 2023. Eligible observational studies with a diagnosis of sarcopenia were included. The Newcastle-Ottawa Scale was utilized for quality assessment. For data synthesis, a random-effects model was used, and the Mantel-Haenszel method was used for pooled estimates. RESULTS: Of the 7685 articles screened, 37 met the inclusion criteria. Statistically significant differences in the levels of IL-1ß, IL-6 and IL-10 were detected in sarcopenia patients. Specifically, IL-1ß (95 % CI: 0.33 [0.12, 0.54], P < 0.05), IL-6 (95 % CI: 0.91 [0.59, 1.24], P < 0.05), and IL-10 (95 % CI: 0.11 [0.07,0.15], P < 0.05) were detected. However, no significant associations were found between serum IL-4 (95 % CI: 0.36 [-0.18, 0.42], P = 0.44), IL-8 (95 % CI: -1.05 [-3.06, 0.95], P = 0.3), IL-12 (95 % CI: -3.92 [-8.32,0.48], P = 0.08) or IL-17 (95 % CI: 0.22 [-2.43, 2.88], P = 0.87) and sarcopenia. Subgroup analysis showed no significant difference in IL-6 (95 % CI: -0.03 [-0.72, 0.66], P = 0.93) and IL-10 (95 % CI: 0.1 [-0.44, 0.64], P = 0.72) among patients with European standard sarcopenia. CONCLUSIONS: Inflammation plays a role in sarcopenia, and the serum levels of IL-1ß, IL-6, and IL-10 are associated with sarcopenia. Further research is needed to clarify these associations. CLINICAL TRIALS REGISTRATION NUMBER: CRD42024506656.

Interleukin 25 promotes muscle regeneration in sarcopenia by regulating macrophage-mediated Sonic Hedgehog signaling.

OBJECTIVE: Sarcopenia manifests as a chronic, low-level inflammation along with multiple inflammatory cells infiltration. Interleukin (IL)-25 can regulate the function of macrophages. However, the specific role and mechanisms through which IL-25 functions in sarcopenia are still not fully understood and require further investigation. METHODS: Aged mice were utilized as sarcopenia models and examined the expression of inflammatory factors. To investigate the effects of IL-25 on sarcopenia, the model mice received IL-25 treatment and underwent in vivo adoptive transfer of IL-25-induced macrophages. Meanwhile, RAW264.7 cells, bone marrow-derived macrophages, satellite cells and C2C12 cells were used in vitro. Shh insufficiency was induced through intramuscular administration of SHH-shRNA adenoviruses. Then, various assays including scratch wound, cell counting kit-8 and Transwell assays, as well as histological staining and molecular biological methods, were conducted. RESULTS: Aged mice exhibited an accelerated decline in muscle strength and mass, along with an increased muscle lipid droplets and macrophage infiltration, and decreased IL-25 levels compared to the young group. IL-25 therapy and the transfer of IL-25-preconditioned macrophages could improve these conditions by promoting M2 macrophage polarization in vivo as well as in vitro. M2 macrophage conditioned medium enhanced satellite cell proliferation and migration, as well as the vitality, migration, and differentiation of C2C12 cells in vitro. Furthermore, IL-25 enhanced Shh expression in macrophages in vitro, and activated the Shh signaling pathway in muscle tissue of aged mice, which could be suppressed by either the inhibitor cyclopamine or Shh knockdown. Mechanistic studies showed that Shh insufficiency suppressed the activation of Akt/mTOR signaling pathway in muscle tissue of aged mice. CONCLUSION: IL-25 promotes the secretion of Shh by M2 macrophages and activates the Shh/Akt/mTOR signaling pathway, which improves symptoms and function in sarcopenia mice. This suggests that IL-25 has potential as a therapeutic agent for treating sarcopenia.

The Self-growth Process of Hospice Volunteers in Ningbo, China.

Objective: The development process of self-growth among Chinese hospice volunteers is poorly understood. This study aimed to explore and delineate their dynamic progression toward self-growth. Methods: This qualitative study used grounded theory to analyze semi-structured interview data using individual in-depth face-to-face interviews with 15 volunteers at a hospice care center in Ningbo, China, between January 2021 and January 2022. Data analysis was based on the open, axial, and selective coding stages of grounded theory and used the constant comparative method. Results: From the interview data, we extracted 1 core category (Death awakening life), 4 categories, and 19 subcategories that pertained to the process of self-growth. The 4 categories delineated the process of self-growth; respondents progressed through self-salvation, self-reflection, self-healing, and self-transcendence stages. The 19 subcategories are introduced and illustrated with interview extracts. Conclusions: The study findings can inform the development of training projects aimed at improving hospice care volunteer services.