Unraveling the relationship between high-sensitivity C-reactive protein and frailty: evidence from longitudinal cohort study and genetic analysis.

BACKGROUND: This study aimed to investigate the association of high-sensitivity C-reactive protein (hs-CRP) with incident frailty as well as its effects on pre-frailty progression and regression among middle-aged and older adults. METHODS: Based on the frailty index (FI) calculated with 41 items, 6890 eligible participants without frailty at baseline from China Health and Retirement Longitudinal Study (CHARLS) were categorized into health, pre-frailty, and frailty groups. Logistic regression models were used to estimate the longitudinal association between baseline hs-CRP and incident frailty. Furthermore, a series of genetic approaches were conducted to confirm the causal relationship between CRP and frailty, including Linkage disequilibrium score regression (LDSC), pleiotropic analysis, and Mendelian randomization (MR). Finally, we evaluated the association of hs-CRP with pre-frailty progression and regression. RESULTS: The risk of developing frailty was 1.18 times (95% CI: 1.03-1.34) higher in participants with high levels of hs-CRP at baseline than low levels of hs-CRP participants during the 3-year follow-up. MR analysis suggested that genetically determined hs-CRP was potentially positively associated with the risk of frailty (OR: 1.06, 95% CI: 1.03-1.08). Among 5241 participants with pre-frailty at baseline, we found pre-frailty participants with high levels of hs-CRP exhibit increased odds of progression to frailty (OR: 1.39, 95% CI: 1.09-1.79) and decreased odds of regression to health (OR: 0.84, 95% CI: 0.72-0.98) when compared with participants with low levels of hs-CRP. CONCLUSIONS: Our results suggest that reducing systemic inflammation is significant for developing strategies for frailty prevention and pre-frailty reversion in the middle-aged and elderly population.

PKM2 is a Novel Osteoporosis-Associated Protein in Chinese.

Purpose:Osteoporosis is characterized by low bone mineral density (BMD) and high risk of osteoporotic fracture (OF). Peripheral blood monocytes (PBM) can differentiate into osteoclasts to resorb bone. This study was to identify PBM-expressed proteins significant for osteoporosis in Chinese Han elderly population (>65 years), and focused on two phenotypes of osteoporosis: low BMD and OF. METHODS: Label-free quantitative proteomics was employed to profile PBM proteome and to identify differentially expressed proteins (DEPs) between OF (N=27) vs. non-fractured (NF, N=24) subjects and between low BMD (N=12) vs. high BMD (N=12) subjects in women. Western blotting (WB) was conducted to validate differential expression, and ELISA to evaluate translational value for secretory protein of interest. RESULTS: We discovered 59 DEPs with fold change (FC)>1.3 (P<1×10-5), and validated the significant up-regulation of pyruvate kinase isozyme 2 (PKM2) with osteoporosis (P<0.001). PKM2 protein upregulation with OF was replicated with PBM in men (P=0.04). Plasma PKM2 protein level was significantly elevated with OF in an independent sample (N=100, FC=1.68, P=0.01). Pursuant functional assays showed that extracellular PKM2 protein supplement not only promoted monocyte trans-endothelial migration, growth, and osteoclast differentiation (marker gene expression), but also inhibited osteoblast growth, differentiation (ALP gene expression), and activity. CONCLUSION: The above findings suggest that PKM2 protein is a novel osteoporosis-associated functional protein in Chinese Han elderly population. It may serve as a risk biomarker and drug target for osteoporosis.

High sensitivity C-reactive protein and prediabetes progression and regression in middle-aged and older adults: A prospective cohort study.

BACKGROUND: This study aimed to investigate the effect of systemic inflammation, assessed by high sensitivity C-reactive protein (hs-CRP) levels, on prediabetes progression and regression in middle-aged and older adults based on the China Health and Retirement Longitudinal Study (CHARLS). METHODS: Participants with prediabetes from CHARLS were followed up 4 years later with blood samples collected for measuring fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). The level of hs-CRP was assessed at baseline and categorized into tertiles (low, middle, and high groups). Prediabetes at baseline and follow-up was defined primarily according to the American Diabetes Association (ADA) criteria. Logistic regression models were used to estimate the odds ratios (ORs) and confidence intervals (CIs). We also performed stratified analyses according to age, gender, BMI, the presence of hypertension, and the disease history of heart disease and dyslipidemia and sensitivity analyses excluding a subset of participants with incomplete data. RESULTS: Of the 2,874 prediabetes included at baseline, 834 participants remained as having prediabetes, 146 progressed to diabetes, and 1,894 regressed to normoglycemia based on ADA criteria with a 4 year follow-up. After multivariate logistics regression analysis, prediabetes with middle (0.67-1.62 mg/L) and high (>1.62 mg/L) hs-CRP levels had an increased incidence of progressing to diabetes compared with prediabetes with low hs-CRP levels (<0.67 mg/L; OR = 1.846, 95%CI: 1.129-3.018; and OR = 1.632, 95%CI: 0.985-2.703, respectively), and the incidence of regressing to normoglycemia decreased (OR = 0.793, 95%CI: 0.645-0.975; and OR = 0.769, 95%CI: 0.623-0.978, respectively). Stratified analyses and sensitivity analyses showed consistent results. CONCLUSIONS: Low levels of hs-CRP are associated with a high incidence of regression from prediabetes to normoglycemia and reduced odds of progression to diabetes.

Effects of static magnetic field on the sulfate metabolic pathway involved in Magnetospirillum magneticum AMB-1 cell growth and magnetosome formation.

AIMS: Magnetotactic bacteria (MTB) can use their unique intracellular magnetosome organelles to swim along the Earth's magnetic field. They play important roles in the biogeochemical cycles of iron and sulfur. Previous studies have shown that the applied magnetic fields could affect the magnetosome formation and antioxidant defense systems in MTB. However, the molecular mechanisms by which magnetic fields affect MTB cells remain unclear. We aim to better understand the dark at 28°C-29°C for 20 h, as shownthe interactions between magnetic fields and cells, and the mechanism of MTB adaptation to magnetic field at molecular levels. METHODS AND RESULTS: We performed microbiological, transcriptomic, and genetic experiments to analyze the effects of a weak static magnetic field (SMF) exposure on the cell growth and magnetosome formation in the MTB strain Magnetospirillum magneticum AMB-1. The results showed that a 1.5 mT SMF significantly promoted the cell growth but reduced magnetosome formation in AMB-1, compared to the geomagnetic field. Transcriptomic analysis revealed decreased expression of genes primarily involved in the sulfate reduction pathway. Consistently, knockout mutant lacking adenylyl-sulfate kinase CysC did no more react to the SMF and the differences in growth and Cmag disappeared. Together with experimental findings of increased reactive oxidative species in the SMF-treated wild-type strain, we proposed that cysC, as a key gene, can participate in the cell growth and mineralization in AMB-1 by SMF regulation. CONCLUSIONS: This study suggests that the magnetic field exposure can trigger a bacterial oxidative stress response involved in AMB-1 growth and magnetosome mineralization by regulating the sulfur metabolism pathway. CysC may serve as a pivotal enzyme in mediating sulfur metabolism to synchronize the impact of SMF on both growth and magnetization of AMB-1.

The TorRS two component system regulates expression of TMAO reductase in response to high hydrostatic pressure in Vibrio fluvialis.

High hydrostatic pressure (HHP) regulated gene expression is one of the most commonly adopted strategies for microbial adaptation to the deep-sea environments. Previously we showed that the HHP-inducible trimethylamine N-oxide (TMAO) reductase improves the pressure tolerance of deep-sea strain Vibrio fluvialis QY27. Here, we investigated the molecular mechanism of HHP-responsive regulation of TMAO reductase TorA. By constructing torR and torS deletion mutants, we demonstrated that the two-component regulator TorR and sensor TorS are responsible for the HHP-responsive regulation of torA. Unlike known HHP-responsive regulatory system, the abundance of torR and torS was not affected by HHP. Complementation of the ΔtorS mutant with TorS altered at conserved phosphorylation sites revealed that the three sites were indispensable for substrate-induced regulation, but only the histidine located in the alternative transmitter domain was involved in pressure-responsive regulation. Taken together, we demonstrated that the induction of TMAO reductase by HHP is mediated through the TorRS system and proposed a bifurcation of signal transduction in pressure-responsive regulation from the substrate-induction. This work provides novel knowledge of the pressure regulated gene expression and will promote the understanding of the microbial adaptation to the deep-sea HHP environment.

Tepidibacter hydrothermalis sp. nov., a novel anaerobic bacterium isolated from a deep-sea hydrothermal vent.

A novel anaerobic heterotrophic bacterium, designated strain SWIR-1T, was isolated from a deep-sea hydrothermal vent field sample collected from the Southwest Indian Ridge at a depth of 2700 m. Phylogenetic analysis indicated that strain SWIR-1T belongs to the genus Tepidibacter, and the most closely related species are Tepidibacter mesophilus B1T (99.1 % 16S rRNA gene sequence similarity), Tepidibacter formicigenes DV1184T (94.6 %) and Tepidibacter thalassicus SC562T (93.9 %). Strain SWIR-1T shares 77.3-87.2 % average nucleotide identity and 21.5-35.7 % digital DNA-DNA hybridization values with the three type strains of Tepidibacter species. Cells of strain SWIR-1T were Gram-stain-positive, motile, short straight rods. Endospores were observed in stationary-phase cells when grown on Thermococcales rich medium. Strain SWIR-1T grew at 15-45 °C (optimum, 30°C), at pH 5.5-8.0 (optimum, pH 7.0) and with 1.0-6.0 % (w/v) NaCl (optimum, 2.0 %). Substrates utilized by strain SWIR-1T included complex proteinaceous, chitin, starch, lactose, maltose, fructose, galactose, glucose, rhamnose, arabinose, ribose, alanine, glycine and glycerol. The major fermentation products from glucose were acetate, lactate, H2 and CO2. Elemental sulphur, sulphate, thiosulphate, sulphite, fumarate, nitrate, nitrite and FeCl3 are not used as terminal electron acceptors. The main cellular fatty acids consisted of iso-C15 : 0 (28.4 %), C15 : 1 iso F (15.4 %) and C16 : 0 (9.8 %). The major polar lipids were phospholipids and glycolipids. No respiratory quinones were detected. Genomic comparison revealed a distinctive blended gene cluster comprising hyb-tat-hyp genes, which play a crucial role in the synthesis, maturation, activation and export of NiFe-hydrogenase. Based on the phylogenetic analysis, genomic, physiologic and chemotaxonomic characteristics, strain SWIR-1T is considered to represent a novel species within the genus Tepidibacter, for which the name Tepidibacter hydrothermalis sp. nov. is proposed. The type strain is strain SWIR-1T (=DSM 113848T=MCCC 1K07078T).

Parasedimentitalea psychrophila sp. nov., a psychrophilic bacterium isolated from deep-sea sediment.

A novel bacterium, strain QS115T, was isolated from deep-sea sediment collected from the South China Sea at a depth of 1151 m. Phylogenetic analyses based on 16S rRNA gene sequences indicated that QS115T was most closely related to Parasedimentitalea marina W43T, with similarity of 98.21 %. Strain QS115T shared 82.39 % average nucleotide identity, 26.3 % digital DNA-DNA hybridization and 85.32 % average amino acid identity with P. marina W43T. Cells of strain QS115T were Gram-stain-negative, rod-shaped and grew optimally at 10 °C, pH 7.5 and 2 % (w/v) NaCl. The principal fatty acids were summed feature 8 (C18 : 1 ω7c/ω6c), the major respiratory quinone was ubiquinone-10 and predominant polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, glycophospholipid, phosphatidylglycerol and phosphatidylcholine. Polyphasic analyses of physiological and phenotypic characteristics and genomic studies suggested that strain QS115T represents a novel species of the genus Parasedimentitalea, for which the name Parasedimentitalea psychrophila sp. nov. is proposed (type strain QS115T=MCCC 1K04395T=JCM 34219T).

Genome analysis of Tepidibacter sp. SWIR-1, an anaerobic endospore-forming bacterium isolated from a deep-sea hydrothermal vent.

Tepidibacter sp. SWIR-1, a putative new species isolated from deep-sea hydrothermal vent field on the Southwest Indian Ridge (SWIR), is an anaerobic, mesophilic and endospore-forming bacterium belonging to the family Peptostreptococcaceae. In this study, we present the complete genome sequence of strain SWIR-1, consists of a single circular chromosome comprising 4,122,966 nucleotides with 29.25% G + C content and a circular plasmid comprising 38,843 nucleotides with 29.46% G + C content. In total, 3861 protein coding genes, 104 tRNA genes and 46 rRNA genes were obtained. SWIR-1 genome contains numerous genes related to sporulation and germination. Compared with the other three Tepidibacter species, SWIR-1 contained more spore germination receptor proteins. In addition, SWIR-1 contained more genes involved in chemotaxis and two-component systems than other Tepidibacter species. These results indicated that SWIR-1 has developed versatile adaptability to the Southwest Indian Ridge hydrothermal vent environment. The genome of strain SWIR-1 will be helpful for further understanding adaptive strategies used by bacteria dwelling in the deep-sea hydrothermal vent environments of different oceans.

Bioluminescence Contributes to the Adaptation of Deep-Sea Bacterium Photobacterium phosphoreum ANT-2200 to High Hydrostatic Pressure.

Bioluminescence is a common phenomenon in nature, especially in the deep ocean. The physiological role of bacterial bioluminescence involves protection against oxidative and UV stresses. Yet, it remains unclear if bioluminescence contributes to deep-sea bacterial adaptation to high hydrostatic pressure (HHP). In this study, we constructed a non-luminescent mutant of ΔluxA and its complementary strain c-ΔluxA of Photobacterium phosphoreum ANT-2200, a deep-sea piezophilic bioluminescent bacterium. The wild-type strain, mutant and complementary strain were compared from aspects of pressure tolerance, intracellular reactive oxygen species (ROS) level and expression of ROS-scavenging enzymes. The results showed that, despite similar growth profiles, HHP induced the accumulation of intracellular ROS and up-regulated the expression of ROS-scavenging enzymes such as dyp, katE and katG, specifically in the non-luminescent mutant. Collectively, our results suggested that bioluminescence functions as the primary antioxidant system in strain ANT-2200, in addition to the well-known ROS-scavenging enzymes. Bioluminescence contributes to bacterial adaptation to the deep-sea environment by coping with oxidative stress generated from HHP. These results further expanded our understanding of the physiological significance of bioluminescence as well as a novel strategy for microbial adaptation to a deep-sea environment.

Insight into the metabolic potential and ecological function of a novel Magnetotactic Nitrospirota in coral reef habitat.

Magnetotactic bacteria (MTB) within the Nitrospirota phylum play important roles in biogeochemical cycles due to their outstanding ability to biomineralize large amounts of magnetite magnetosomes and intracellular sulfur globules. For several decades, Nitrospirota MTB were believed to only live in freshwater or low-salinity environments. While this group have recently been found in marine sediments, their physiological features and ecological roles have remained unclear. In this study, we combine electron microscopy with genomics to characterize a novel population of Nitrospirota MTB in a coral reef area of the South China Sea. Both phylogenetic and genomic analyses revealed it as representative of a novel genus, named as Candidatus Magnetocorallium paracelense XS-1. The cells of XS-1 are small and vibrioid-shaped, and have bundled chains of bullet-shaped magnetite magnetosomes, sulfur globules, and cytoplasmic vacuole-like structures. Genomic analysis revealed that XS-1 has the potential to respire sulfate and nitrate, and utilize the Wood-Ljungdahl pathway for carbon fixation. XS-1 has versatile metabolic traits that make it different from freshwater Nitrospirota MTB, including Pta-ackA pathway, anaerobic sulfite reduction, and thiosulfate disproportionation. XS-1 also encodes both the cbb3-type and the aa3-type cytochrome c oxidases, which may function as respiratory energy-transducing enzymes under high oxygen conditions and anaerobic or microaerophilic conditions, respectively. XS-1 has multiple copies of circadian related genes in response to variability in coral reef habitat. Our results implied that XS-1 has a remarkable plasticity to adapt the environment and can play a beneficial role in coral reef ecosystems.

Association of Self-Reported Sleep Characteristics and Hip Fracture: Observational and Mendelian Randomization Studies.

Previous observational studies on the relationship between sleep characteristics and fracture have yielded contradictory results. The goal of this study was to replicate the findings in a large longitudinal cohort and then conduct a Mendelian randomization (MR) analysis to infer the causality between sleep behaviors and fracture risk. Based on data from the China Health and Retirement Longitudinal Study (CHARLS) including 17,708 participants, we found that individuals with short sleep duration (<5 h) (OR [odds ratio] = 1.62, 95% CI: 1.07-2.44) or restless sleep (OR = 1.55, 95% CI: 1.10-2.19) have a higher risk of hip fracture. A U-shaped relationship between nighttime sleep duration and hip fracture risk (p-nonlinear = 0.01) was observed using restricted cubic spline regression analysis. Through joint effect analysis, we found that participants with short sleep duration (<5 h) combined with midday napping could significantly decrease hip fracture incidence. We further inferred the causal relationship between self-reported sleep behaviors and hip fracture using the MR approach. Among four sleep phenotypic parameters (sleep duration, daytime napping, chronotype, and insomnia), we found a modest causal relationship between sleep duration and fracture (OR = 0.69, 95% CI: 0.48 to 0.99, p = 0.04). However, no causal relationship was observed for other sleep traits. In conclusion, our findings suggest that short sleep duration has a potential detrimental effect on hip fracture. Improving sleep patterns is of significance for developing hip fracture preventive strategies in the middle-aged and the elderly populations.

Piezophilic Phenotype Is Growth Condition Dependent and Correlated with the Regulation of Two Sets of ATPase in Deep-Sea Piezophilic Bacterium Photobacterium profundum SS9.

Alteration of respiratory components as a function of pressure is a common strategy developed in deep-sea microorganisms, presumably to adapt to high hydrostatic pressure (HHP). While the electron transport chain and terminal reductases have been extensively studied in deep-sea bacteria, little is known about their adaptations for ATP generation. In this study, we showed that the deep-sea bacterium Photobacterium profundum SS9 exhibits a more pronounced piezophilic phenotype when grown in minimal medium supplemented with glucose (MG) than in the routinely used MB2216 complex medium. The intracellular ATP level varied with pressure, but with opposite trends in the two culture media. Between the two ATPase systems encoded in SS9, ATPase-I played a dominant role when cultivated in MB2216, whereas ATPase-II was more abundant in the MG medium, especially at elevated pressure when cells had the lowest ATP level among all conditions tested. Further analyses of the ΔatpI, ΔatpE1 and ΔatpE2 mutants showed that disrupting ATPase-I induced expression of ATPase-II and that the two systems are functionally redundant in MB2216. Collectively, we provide the first examination of the differences and relationships between two ATPase systems in a piezophilic bacterium, and expanded our understanding of the involvement of energy metabolism in pressure adaptation.

Crassaminicella indica sp. nov., a novel thermophilic anaerobic bacterium isolated from a deep-sea hydrothermal vent.

A novel moderately thermophilic heterotrophic bacterium, designated strain 143-21T, was isolated from a deep-sea hydrothermal chimney sample collected from the Central Indian Ridge at a depth of 2 440 m. Phylogenetic analysis indicated that strain 143-21T belongs to the genus Crassaminicella. It was most closely related to Crassaminicella thermophila SY095T (96.79 % 16S rRNA gene sequence similarity) and Crassaminicella profunda Ra1766HT (96.52 %). Genomic analysis showed that strain 143-21T shares 79.79-84.45 % average nucleotide identity and 23.50-29.20 % digital DNA-DNA hybridization with the species of the genus Crassaminicella, respectively. Cells were rod-shaped, non-motile, Gram-positive-staining. Terminal endospores were observed in stationary-phase cells when strain 143-21T was grown on Thermococcales rich medium. Strain 143-21T was able to grow at 30-60 °C (optimum, 50 °C), pH 6.5-8.5 (optimum, pH 7.0) and in 1.0-7.0 % NaCl (w/v; optimum 2.0 %, w/v). Strain 143-21T utilized fructose, glucose, maltose, mannose, ribose, N-acetyl-d-(+)-glucosamine and casamino acids, as well as amino acids including glutamate, lysine, histidine and cysteine. The main fermentation products from glucose were acetate (2.07 mM), H2 and CO2. It did not reduce elemental sulphur, sulphate, thiosulphate, sulphite, fumarate, nitrate, nitrite and Fe (III). The predominant cellular fatty acids were C14 : 0 (48.8 %), C16 : 0 (12.9 %), and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c; 10.2 %). The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol, as well as two unidentified phospholipids and four unidentified aminolipids. No respiratory quinones were detected. Based on its phylogenetic analysis and physiological characteristics, strain 143-21T is considered to represent a novel species of the genus Crassaminicella, for which the name Crassaminicella indica sp. nov. is proposed. The type strain is strain 143-21T (=DSM 114408T= MCCC 1K06400T).

A novel long non-coding RNA, lnc-RNU12, influences the T-cell cycle via c-JUN and CCNL2 in rheumatoid arthritis.

OBJECTIVES: Long non-coding RNAs (lncRNAs) play important roles in RA pathogenesis. However, specific lncRNAs that regulate gene expression in RA pathogenesis are poorly known. This study was undertaken to characterize a novel lncRNA (lnc-RNU12) that has a lower-than-normal expression level in RA patients. METHODS: We performed initial genome-wide lncRNA microarray screening in peripheral blood mononuclear cells from 28 RA cases and 18 controls. Multiple methods were used to validate the detected associations between lncRNAs and RA. Furthermore, we identified the source and characteristics of the highlighted lncRNAs, detected the target genes, and determined the functional effect on immune cells through lncRNA knock-down in Jurkat T cell lines. RESULTS: lnc-RNU12 was downregulated in peripheral blood mononuclear cells and T cell subtypes of RA patients and was genetically associated with RA risk. lnc-RNU12 mediates the effect of microbiome alterations on RA risk. Activation of T cells caused low expression of lnc-RNU12. Knock-down of lnc-RNU12 in Jurkat T cells caused cell cycle S-phase arrest and altered the expression of protein-coding genes related to the cell cycle and apoptosis (e.g. c-JUN, CCNL2, CDK6, MYC, RNF40, PKM, VPS35, DNAJB6 and FLCN). Finally, c-JUN and CCNL2 were identified as target genes of lnc-RNU12 at the mRNA and protein expression levels. RNA-binding protein immunoprecipitation assays verified the interaction between lnc-RNU12 and the two proteins (c-Jun and cyclin L2) in Jurkat cells. CONCLUSIONS: Our study suggested that lnc-RNU12 was involved in the pathogenesis of RA by influencing the T cell cycle by targeting c-JUN and CCNL2.

Template-Free Assembly of Functional RNAs by Loop-Closing Ligation.

The first ribozymes are thought to have emerged at a time when RNA replication proceeded via nonenzymatic template copying processes. However, functional RNAs have stable folded structures, and such structures are much more difficult to copy than short unstructured RNAs. How can these conflicting requirements be reconciled? Also, how can the inhibition of ribozyme function by complementary template strands be avoided or minimized? Here, we show that short RNA duplexes with single-stranded overhangs can be converted into RNA stem loops by nonenzymatic cross-strand ligation. We then show that loop-closing ligation reactions enable the assembly of full-length functional ribozymes without any external template. Thus, one can envisage a potential pathway whereby structurally complex functional RNAs could have formed at an early stage of evolution when protocell genomes might have consisted only of collections of short replicating oligonucleotides.

Metagenomic and Microscopic Analysis of Magnetotactic Bacteria in Tangyin Hydrothermal Field of Okinawa Trough.

Magnetotactic bacteria (MTB) have been found in a wide variety of marine habitats, ranging from intertidal sediments to deep-sea seamounts. Deep-sea hydrothermal fields are rich in metal sulfides, which are suitable areas for the growth of MTB. However, MTB in hydrothermal fields have never been reported. Here, the presence of MTB in sediments from the Tangyin hydrothermal field was analyzed by 16S rRNA gene amplicon analysis, metagenomics, and transmission electron microscopy. Sequencing 16S rRNA gene yielded a total of 709 MTB sequences belonging to 20 OTUs, affiliated with Desulfobacterota, Alphaproteobacteria, and Nitrospirae. Three shapes of magnetofossil were identified by transmission electron microscopy: elongated-prismatic, bullet-shaped, and cuboctahedron. All of these structures were composed of Fe3O4. A total of 121 sequences were found to be homologous to the published MTB magnetosome-function-related genes, and relevant domains were identified. Further analysis revealed that diverse MTB are present in the Tangyin hydrothermal field, and that multicellular magnetotactic prokaryote (MMPs) might be the dominant MTB.

A Novel Isolate of Spherical Multicellular Magnetotactic Prokaryotes Has Two Magnetosome Gene Clusters and Synthesizes Both Magnetite and Greigite Crystals.

Multicellular magnetotactic prokaryotes (MMPs) are a unique group of magnetotactic bacteria that are composed of 10-100 individual cells and show coordinated swimming along magnetic field lines. MMPs produce nanometer-sized magnetite (Fe3O4) and/or greigite (Fe3S4) crystals-termed magnetosomes. Two types of magnetosome gene cluster (MGC) that regulate biomineralization of magnetite and greigite have been found. Here, we describe a dominant spherical MMP (sMMP) species collected from the intertidal sediments of Jinsha Bay, in the South China Sea. The sMMPs were 4.78 ± 0.67 µm in diameter, comprised 14-40 cells helical symmetrically, and contained bullet-shaped magnetite and irregularly shaped greigite magnetosomes. Two sets of MGCs, one putatively related to magnetite biomineralization and the other to greigite biomineralization, were identified in the genome of the sMMP, and two sets of paralogous proteins (Mam and Mad) that may function separately and independently in magnetosome biomineralization were found. Phylogenetic analysis indicated that the sMMPs were affiliated with Deltaproteobacteria. This is the first direct report of two types of magnetosomes and two sets of MGCs being detected in the same sMMP. The study provides new insights into the mechanism of biomineralization of magnetosomes in MMPs, and the evolutionary origin of MGCs.

Body Surface Area (BSA) is a Better Osteoporosis Associated Anthropometric Parameter Than Other Anthropometric Parameters in Elderly Population.

Body surface area (BSA) is widely used for adjusting drug dose, while few studies have yet systematically evaluated its association with osteoporosis and compared its advantage with other anthropometric parameters in osteoporotic risk prediction. A total of 10,021 Chinese individuals aged over 65 years were enrolled in our study. Bone mineral density (BMD) was measured, and demographic information was also collected. Pearson correlation analysis, receiver operating characteristic (ROC) curves and predictive analysis were performed to assess the clinical practice of BSA for osteoporosis. BSA had the strongest correlation with BMD (0.544, p < 0.001) compared with conventional anthropometric indices. Besides, BSA had the highest power in osteoporosis prediction, with an area under the curve (AUC) reaching 0.81. After incorporating BSA into the osteoporosis risk prediction model, the AUC improved from 0.82 to 0.83 (p < 0.01). We found BSA provided additional diagnostic value beyond conventional anthropometric information with continuous and category NRIs were 30.40% (p < 0.01) and 3.29% (p < 0.01), respectively, and the IDI was 1.85% (p < 0.01). BSA was positively associated with osteoporosis and showed superior discriminative ability for osteoporosis risk prediction compared with other anthropometric parameters in the Chinese elderly population.

Identification of novel rheumatoid arthritis-associated MiRNA-204-5p from plasma exosomes.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by infiltration of immune cells in the synovium. However, the crosstalk of immune cells and synovial fibroblasts is still largely unknown. Here, global miRNA screening in plasma exosomes was carried out with a custom microarray (RA patients vs. healthy controls = 9:9). A total of 14 exosomal miRNAs were abnormally expressed in the RA patients. Then, downregulated expression of exosomal miR-204-5p was confirmed in both the replication (RA patients vs. healthy controls = 30:30) and validation groups (RA patients vs. healthy controls = 56:60). Similar to the findings obtained in humans, a decreased abundance of exosomal miR-204-5p was observed in mice with collagen-induced arthritis (CIA). Furthermore, Spearman correlation analysis indicated that plasma exosomal miR-204-5p expression was inversely correlated with disease parameters of RA patients, such as rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein. In vitro, our data showed that human T lymphocytes released exosomes containing large amounts of miR-204-5p, which can be transferred into synovial fibroblasts, inhibiting cell proliferation. Overexpression of miR-204-5p in synovial fibroblasts suppressed synovial fibroblast activation by targeting genes related to cell proliferation and invasion. In vivo assays found that administration of lentiviruses expressing miR-204-5p markedly alleviated the disease progression of the mice with CIA. Collectively, this study identified a novel RA-associated plasma exosomal miRNA-204-5p that mediates the communication between immune cells and synovial fibroblasts and can be used as a potential biomarker for RA diagnosis and treatment.

Clinical effects of cluster technology optimization and innovations on laparoscopic splenectomy and azygoportal disconnection: a single-center retrospective study with 500 consecutive cases.

BACKGROUND: In Asia, laparoscopic splenectomy and azygoportal disconnection (LSD) has been widely regarded as a preferential treatment modality for cirrhotic portal hypertension (PH). However, LSD involves high surgical risk, technical challenges, and many potential postoperative complications. Technology optimization and innovation in LSD aiming to solve to these difficulties has scarcely been reported. In this retrospective study, we aimed to evaluate the clinical therapeutic effect of our cluster technology optimization and innovation on LSD for PH. METHODS: From February 2012 to January 2020, 500 patients with cirrhosis who had esophagogastric variceal bleeding and hypersplenism underwent LSD in our department. According to different operation periods, patients were divided into the early-, intermediate-, and late-period groups. We collected information regarding clinical characteristics of all patients as well as their preoperative and postoperative follow-up data. RESULTS: Compared with the early-period group, operation time and postoperative hospital stay were all significantly different and gradually declined from the intermediate- and late-period groups, respectively (all P < 0.05). Intraoperative blood loss of these three groups was gradually decreased, with significant differences (P < 0.05). The incidences of delayed gastric emptying and diarrhea in the late-period group were all significantly lower than those in the early- and intermediate-period groups, respectively (all P < 0.05). Compared with the early-period group, the incidence of variceal re-bleeding was significantly lower in the intermediate- and late-period groups (all P < 0.05). CONCLUSION: Our cluster technology optimization and innovation of LSD not only contributed to faster recovery and fewer complications but also enhanced surgical safety for patients. It is worth promoting this approach among patients with EVB and hypersplenism secondary to cirrhotic PH.