A novel variant (p.A524P) in Spastin is responsible for a Chinese family with hereditary spastic paraplegia.

BACKGROUND: Hereditary spastic paraplegia (HSP) represents a group of monogenic neurodegenerative disorders characterized by high clinical and genetic heterogeneity. HSP is characterized by slowly progressing hypertonia of both lower extremities, spastic gait, and myasthenia. The most prevalent autosomal dominant form of HSP, known as spastic paraplegia 4 (SPG4), is attributed to variants in the spastin (SPAST) gene. METHODS AND RESULTS: Here, a Chinese family presenting with spasticity in both legs and a shuffling gait participated in our investigation. Whole exome sequencing of the proband was utilized to identify the genetic lesion in the family. Through data filtering, Sanger sequencing validation, and co-separation analysis, a novel variant (NM_014946.3: c.1669G > C:p.A557P) of SPAST was identified as the genetic lesion of this family. Furthermore, bioinformatic analysis revealed that this variant was deleterious and located in a highly evolutionarily conserved site. CONCLUSION: Our study confirmed the diagnosis of SPG4 in this family, contributing to genetic counseling for families affected by SPG4. Additionally, our study broadened the spectrum of SPAST variants and highlighted the importance of ATPases associated with various cellular activity domains of SPAST.

Sleep patterns, genetic susceptibility, and venous thromboembolism: A prospective study of 384,758 UK Biobank participants.

BACKGROUND: Although healthy sleep patterns have been linked to a lower risk of cardiovascular disease in earlier research, it is unclear how beneficial they are for venous thromboembolism (VTE). AIM: This research aimed to examine the correlation between sleep patterns, genetic susceptibility, and VTE. METHODS: In the UK Biobank cohort, healthy sleep behaviors were defined as early chronotype, 7-8 hours of sleep each day, no snoring, infrequent insomnia, and infrequent daytime sleepiness. Each of the five criteria was given 1 point, creating a healthy sleep score ranging from 0 to 5. Cox proportional hazards regression models were utilized to examine the associations between genetic susceptibility, healthy sleep score and VTE. RESULTS: The UK Biobank study included 384,758 participants aged 56.6 ± 8.0 years. After a median of 11.9 years of follow-up, 8,885 (2.3%) participants were diagnosed with VTE. A healthy sleep score inversely affected VTE risk. For participants with a score of 5, the hazard ratio of VTE was 0.813 (95% confidence interval: 0.758-0.873, P<0.001) compared to those with a score ≤2. Early chronotype, sleeping 7-8 hours each day, infrequent insomnia, and infrequent daytime sleepiness were significantly associated with a 7.9%, 8.3%, 5.1%, and 20.7% lower risk of VTE, respectively. In addition, the correlation between sleep pattern and the incidence of VTE was consistent, regardless of genetic susceptibility (P for interaction = 0.366). CONCLUSIONS: Our secondary analysis of a large-scale prospectively gathered registry revealed that individuals with a healthy sleep pattern are significantly correlated with lower risk of developing VTE, irrespective of genetic susceptibility.

Endothelial γ-protocadherins inhibit KLF2 and KLF4 to promote atherosclerosis.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Laminar shear stress from blood flow, sensed by vascular endothelial cells, protects from ASCVD by upregulating the transcription factors KLF2 and KLF4, which induces an anti-inflammatory program that promotes vascular resilience. Here we identify clustered γ-protocadherins as therapeutically targetable, potent KLF2 and KLF4 suppressors whose upregulation contributes to ASCVD. Mechanistic studies show that γ-protocadherin cleavage results in translocation of the conserved intracellular domain to the nucleus where it physically associates with and suppresses signaling by the Notch intracellular domain. γ-Protocadherins are elevated in human ASCVD endothelium; their genetic deletion or antibody blockade protects from ASCVD in mice without detectably compromising host defense against bacterial or viral infection. These results elucidate a fundamental mechanism of vascular inflammation and reveal a method to target the endothelium rather than the immune system as a protective strategy in ASCVD.

The functional subclasses of AT1 receptor autoantibody in patients with coronary heart disease.

Recently, the identification of autoantibodies (AT1-AA) targeting the second extracellular loop of angiotensin II type 1 receptor (AT1R-ECII) in patients with coronary heart disease (CHD) offers a novel perspective on the interplay between immunity and cardiovascular disease. However, much remains unknown regarding the functional diversity of AT1-AA. In this study, we measured the levels of AT1-AA in the sera of 306 CHD patients and purified AT1-AA from patient's sera (n = 127). The subclasses of AT1-AA were categorized based on their impact on intracellular calcium ([Ca2+]i) levels in mouse arterial smooth muscle cells (MASMCs). Our findings revealed 4 distinct [Ca2+]i response patterns indicating the existence of 4 functional subclasses named H1-, H2-, H3-, and H4-AT1-AA. The correlation analysis demonstrated a positive association between H1-AT1-AA and endogenous coagulation, as well as between H2-AT1-AA and exogenous coagulation; no significant correlation was observed between H3-AT1-AA and the indicators we analyzed. Conversely, H4-AT1-AA exhibited a negative correlation with both leukocyte number and bile acid levels. Logistic regression analysis showed that H2-AT1-AA possessed predictive value for severe CHD. Furthermore, in vitro experiments indicated that both H1- and H2-AT1-AA exerted cytotoxic effects on MASMCs, while H4-AT1-AA increased cell viability. Additionally, an AT1-AA-positive rat model was established by subcutaneously injecting with AT1R-ECII peptide, which produced four similar functional subclasses of rat AT1-AA upon active immunization. This study suggested that classifying different functional subclasses of AT1-AAs can facilitate more accurate evaluation of the condition and prognosis in patients with CHD, thereby providing a novel basis for clinical diagnosis and treatment.

A comprehensive study of Tianma Toutong Tablets from the dual dimensions of quality and efficacy using fingerprint techniques and network pharmacology.

BACKGROUND: The quality of traditional Chinese medicine (TCM) is the prerequisite for ensuring its safe and effective clinical application. With the increasing popularity of TCM worldwide, the quality control of TCM products has become increasingly crucial. Tianma toutong tablet (TMTTT) is mainly used for migraine caused by external wind and cold, blood stasis, or deficiency of blood and nourishment. However, the mechanism of action of TMTTT is still unclear, and there has been a lack of in vitro antioxidant activity research and migraine treatment mechanism research. Therefore, it is urgent to establish a set of comprehensive and effective evaluation methods. RESULTS: three fingerprint profiles were established using HPLC, UV, and DSC analysis methods, and established three digital parameters simple complexity index (SX), simple clarity index (SY), simple complexity clarity ratio (Sω), 22 batches of samples were evaluated using a comprehensive linear quantitative fingerprint method (CLQFM). In addition, the antioxidant activity of the samples was determined using the DPPH method, and the relationship between fingerprint peaks in different fingerprints and antioxidant capacity was explored using Pearson correlation coefficients. Finally, network pharmacological research was conducted to investigate the potential targets, compounds, and pathways involved in the treatment of migraines with TMTTT. The results showed that the 22 batches of samples were classified into different quality grades. TMTTT exhibited good antioxidant activity, the fingerprint-efficacy relationship showed that gastrodin, chlorogenic acid, ferulic acid, imperatorin and isoimperatorin had strong antioxidant capacity, providing directions for the identification of active compounds. A total of 36 core targets were identified and screened by network pharmacology, which AKT serine/threonine kinase 1 (AKT1), albumin (ALB), insulin (INS), tumor necrosis factor (TNF), prostaglandin-endoperoxide synthase 2 (PTGS2) and interleukin-6 (IL-6), and compounds such as ß-sitosterol, chrysophanol, vanillin are the key to the treatment of migraine, providing references for subsequent clinical research and new drug development. SIGNIFICANCE: This study examined the consistency of the quality of TMTTT and the mechanism of action in treating migraines from both quality and efficacy perspectives, providing a favorable direction for further research on TMTTT and offering new ideas for the quality control of TCM compound formulations.

Bridging childhood to adulthood: the impact of early life stress on acute stress responses.

Background: Childhood trauma exerts enduring impacts on the physical and psychological well-being of individuals in adulthood, influencing their daily functioning. This study aims to investigate the impact of childhood trauma on stress recovery in adults, concentrating on heart rate variations during acute stress exposure. Methods: A cohort of 126 participants completed the Childhood Trauma Questionnaire (CTQ) and underwent the Trier Social Stress Test (TSST) to elicit acute stress, with continuous heart rate (HR) monitoring for stress recovery assessment. Results: The results revealed a negative correlation between childhood trauma and stress recovery, prominently observed in instances of emotional neglect and abuse. Individuals with heightened childhood trauma exhibited protracted stress recovery following acute stress exposure. Conclusion: Childhood traumatic experiences were associated with the recovery from acute stress, as indicated by heart rate indices. These findings contribute to the foundational framework for psychological interventions tailored to individuals with a history of childhood trauma.

Intercropping improves maize yield and nitrogen uptake by regulating nitrogen transformation and functional microbial abundance in rhizosphere soil.

Intercropping-driven changes in nitrogen (N)-acquiring microbial genomes and functional expression regulate soil N availability and plant N uptake. However, present data seem to be limited to a specific community, obscuring the viewpoint of entire N-acquiring microbiomes and functions. Taking maize intercropped with legumes (peanut and soybean) and non-legumes (gingelly and sweet potato) as models, we studied the effects of intercropping on N transformations and N-acquiring microbiomes in rhizosphere soil across four maize growth stages. Meanwhile, we compiled promising strategies such as random forest analysis and structural equation model for the exploitation of the associations between microbe-driven N dynamics and soil-plant N trade-offs and maize productivity. Compared with monoculture, maize intercropping significantly increased the denitrification rate of rhizosphere soils across four maize growth stages, net N mineralization in the elongation and flowering stages, and the nitrification rate in the seedling and mature stages. The abundance of most N-acquiring microbial populations was influenced significantly by intercropping patterns and maize growth stages. Soil available N components (NH4+-N, NO3--N, and dissolved organic N content) showed a highly direct effect on plant N uptake, which mainly mediated by N transformations (denitrification rate) and N-acquiring populations (amoB, nirK3, and hzsB genes). Overall, the adaptation of N-acquiring microbiomes to changing rhizosphere micro-environments caused by intercropping patterns and maize development could promote soil N transformations and dynamics to meet demand of maize for N nutrient. This would offer another unique perspective to manage the benefits of the highly N-effective and production-effective intercropping ecosystems.

Series of Viologen-Based Metal-Organic Polyhedra with Photo/Electrochromic Behavior for Inkless Printing and UV Detection.

The fabrication of molecular crystalline materials with fast, multistimuli-responsive behavior and the construction of the corresponding structure-activity relationship are of extraordinary significance for the development of smart materials. In this context, three multistimuli-responsive functional metal-organic polyhedra (MOP), {[Dy2(bcbp)3(NO3)1.5(H2O)7]·Cl4.2·(NO3)0.3·H2O}n (1), {[Dy2(bcbp)4(H2O)8]Cl6}n (2), and {[Eu2(bcbp)4(H2O)10]Cl6·H2O}n (3; bcbp = 1,1'-bis(4-carboxyphenyl)-4,4'-bipyridinium), were successfully prepared and characterized. All of the compounds exhibit rapid and reversible photochromic and electrochromic dual-responsive behaviors. Furthermore, benefiting from the well-defined crystal structure and different responsive behaviors, the photoinduced electron transfer (PIET) process and structure-activity relationship were explored. In addition, considering the excellent photochromic performance, function filter paper and smart organic glass were successfully prepared and used for ink-free printing and UV light detection.

Small regulatory RNA RSaX28 promotes virulence by reinforcing the stability of RNAIII in community-associated ST398 clonotype Staphylococcus aureus.

Staphylococcus aureus (S. aureus) is a notorious pathogen that cause metastatic or complicated infections. Hypervirulent ST398 clonotype strains, remarkably increased in recent years, dominated Community-associated S. aureus (CA-SA) infections in the past decade in China. Small RNAs like RNAIII have been demonstrated to play important roles in regulating the virulence of S. aureus, however, the regulatory roles played by many of these sRNAs in the ST398 clonotype strains are still unclear. Through transcriptome screening and combined with knockout phenotype analysis, we have identified a highly transcribed sRNA, RSaX28, in the ST398 clonotype strains. Sequence analysis revealed that RSaX28 is highly conserved in the most epidemic clonotypes of S. aureus, but its high transcription level is particularly prominent in the ST398 clonotype strains. Characterization of RSaX28 through RACE and Northern blot revealed its length to be 533nt. RSaX28 is capable of promoting the hemolytic ability, reducing biofilm formation capacity, and enhancing virulence of S. aureus in the in vivo murine infection model. Through IntaRNA prediction and EMSA validation, we found that RSaX28 can specifically interact with RNAIII, promoting its stability and positively regulating the translation of downstream alpha-toxin while inhibiting the translation of Sbi, thereby regulating the virulence and biofilm formation capacity of the ST398 clonotype strains. RSaX28 is an important virulence regulatory factor in the ST398 clonotype S. aureus and represents a potential important target for future treatment and immune intervention against S. aureus infections.

Highly Stable Silicon Anode Enabled by a Water-Soluble Tannic Acid Functionalized Dual-Network Binder.

Silicon (Si), a high-capacity electrode material, is crucial for achieving high-energy-density lithium-ion batteries. However, Si suffers from poor cycling stability due to its significant volume changes during operation. In this work, a tannic acid functionalized aqueous dual-network binder with an intramolecular tannic acid functionalized network has been synthesized, which is composed of covalent-cross-linked polyamide and ionic-cross-linked alginate (Alg(Ni)-PAM-TA), and employed as an advanced binder for stabilizing Si anodes. The resultant Alg(Ni)-PAM-TA binder, incorporating diverse functional groups including amide, carboxylic acid, and dynamic hydrogen bonds, can easily interact with both Si nanoparticles and the Cu foil, thereby facilitating the formation of a highly resilient network characterized by exceptional adhesion strength. Moreover, molecular dynamics (MD) simulations indicate that the Alg(Ni)-PAM-TA network shows an increased intramolecular hydrogen bond number with increasing concentration of TA and a decreased intramolecular hydrogen bond between PAM and Alg as a result of the aggregation behavior of tannic acids themselves. Consequently, the binder significantly enhances the Si electrode's integrity throughout repeated charge/discharge cycles. At a current density of 0.84 A g-1, the Si electrode retains a capacity of 1863.4 mAh g-1 after 200 cycles. This aqueous binder functionalized with the intramolecular network via the incorporation of TA molecules holds great promise for the development of high-energy-density lithium-ion batteries.

Exceptional Magnetocaloric Responses in a Gadolinium Silicate with Strongly Correlated Spin Disorder for Sub-Kelvin Magnetic Cooling.

The development of magnetocaloric materials with a significantly enhanced volumetric cooling capability is highly desirable for the application of adiabatic demagnetization refrigerators in confined spatial environments. Here, the thermodynamic characteristics of a magnetically frustrated spin-7/2 Gd9.33[SiO4]6O2 is presented, which exhibits strongly correlated spin disorder below ≈1.5 K. A quantitative model is proposed to describe the magnetization results by incorporating nearest-neighbor Heisenberg antiferromagnetic and dipolar interactions. Remarkably, the recorded magnetocaloric responses are unprecedentedly large and applicable below 1.0 K. It is proposed that the S = 7/2 spin liquids serve as versatile platforms for investigating high-performance magnetocaloric materials in the sub-kelvin regime, particularly those exhibiting a superior cooling power per unit volume.

Emerging Trends in Teledermatology Research: A Scientometric Analysis from 2002 to 2021.

Background: With advances in technology, teledermatology (TD) research has increased. However, an updated comprehensive quantitative analysis of TD research, especially one that identifies emerging trends of TD research in the coronavirus disease 2019 (COVID-19) era, is lacking. Objective: To conduct a scientometric analysis of TD research documents between 2002 and 2021 and explore the emerging trends. Methods: CiteSpace was used to perform scientometric analysis and yielded visualized network maps with corresponding metric values. Emerging trends were identified mainly through burst detection of keywords/terms, co-cited reference clustering analysis, and structural variability analysis (SVA). Results: A total of 932 documents, containing 27,958 cited references were identified from 2002 to 2021. Most TD research was published in journals from the "Dermatology" and "Health Care Sciences & Services" categories. American, Australian, and European researchers contributed the most research and formed close collaborations. Keywords/terms with strong burst values to date were "primary care," "historical perspective," "emerging technique," "improve access," "mobile teledermoscopy (TDS)," "access," "skin cancer," "telehealth," "recent finding," "artificial intelligence (AI)," "dermatological care," and "dermatological condition." Co-cited reference clustering analysis showed that the recently active cluster labels included "COVID-19 pandemic," "skin cancer," "deep neural network," and "underserved population." The SVA identified two reviews (Tognetti et al. and Mckoy et al.) that may be highly cited in the future. Conclusion: During and after the COVID-19 era, emerging trends in research on TD (especially mobile TDS) may be related to skin cancer and AI as well as further exploration of primary care in underserved areas.

Copublication promotes dissemination hypertension guidelines: a retrospective cohort study.

To evaluate the impact of copublication on hypertension-related clinical practice guidelines' citation, we searched the Web of Science Core Collection and guide.medlive.cn until 31 December 2017 using the terms "hypertension" and "guideline". The copublished group was matched with the noncopublished group at a 1:2 ratio. Primary outcomes were total citations and citations within the first five years after publication. Secondary outcomes included the adjusted impact factor ratio (excluding copublished guidelines) to the actual impact factor of the journal. Altmetric scores were compared using Altmetric explorer data. 21 copublished and 42 noncopublished guidelines were included. The copublished group had higher median current total citations [387.0 (90.0, 1806.0) vs 70.5 (23.25, 158.25)], and higher median citations at one, two, three, four, and five years [7.0 (0.5, 58.5) vs 1.0 (0.0, 5.5), 33.0 (14.0, 142.0) vs 5.5 (1.75, 26.25), 46.0 (24.5, 216.0) vs 10.5 (3, 25.75), 50.0 (19.0, 229.0) vs 9.0 (3.0, 19.0), 52.0 (13.5, 147.0) vs 7.0 (2.0, 20.0), all p < 0.05]. The adjusted IF analysis showed that if they had not copublished the guidelines, 10 of 24 and 11 of 24 journals would have had a lower IF in the first and second years. Median altmetric scores were significantly higher for copublished guidelines [38.5 (9.5, 90.5) vs 3.5 (1.0, 9.0)] (p < 0.05). Copublication is associated with a higher citation frequency of hypertension guidelines and may increase the journal IF. Positive impacts extend beyond academia, benefiting society through broader guideline application and dissemination. This facilitates broader application of guidelines and promotes their dissemination. We conducted a retrospective cohort study to demonstrate how copublication promotes the dissemination of hypertension guidelines.

Spatiotemporal adaptive attention graph convolution network for city-level air quality prediction.

Air pollution is a leading cause of human diseases. Accurate air quality predictions are critical to human health. However, it is difficult to extract spatiotemporal features among complex spatiotemporal dependencies effectively. Most existing methods focus on constructing multiple spatial dependencies and ignore the systematic analysis of spatial dependencies. We found that besides spatial proximity stations, functional similarity stations, and temporal pattern similarity stations, the shared spatial dependencies also exist in the complete spatial dependencies. In this paper, we propose a novel deep learning model, the spatiotemporal adaptive attention graph convolution model, for city-level air quality prediction, in which the prediction of future short-term series of PM2.5 readings is preferred. Specifically, we encode multiple spatiotemporal dependencies and construct complete spatiotemporal interactions between stations using station-level attention. Among them, we design a Bi-level sharing strategy to extract shared inter-station relationship features between certain stations efficiently. Then we extract multiple spatiotemporal features with multiple decoders, which it is extracted from the complete spatial dependencies between stations. Finally, we fuse multiple spatiotemporal features with a gating mechanism for multi-step predictions. Our model achieves state-of-the-art experimental results in several real-world datasets.

Detection of low-frequency mutations in clinical samples by increasing mutation abundance via the excision of wild-type sequences.

The efficiency of DNA-enrichment techniques is often insufficient to detect mutations that occur at low frequencies. Here we report a DNA-excision method for the detection of low-frequency mutations in genomic DNA and in circulating cell-free DNA at single-nucleotide resolution. The method is based on a competitive DNA-binding-and-digestion mechanism, effected by deoxyribonuclease I (DNase) guided by single-stranded phosphorothioated DNA (sgDNase), for the removal of wild-type DNA strands. The sgDNase can be designed against any wild-type DNA sequences, allowing for the uniform enrichment of all the mutations within the target-binding region of single-stranded phosphorothioated DNA at mild-temperature conditions. Pretreatment with sgDNase enriches all mutant strands with initial frequencies down to 0.01% and leads to high discrimination factors for all types of single-nucleotide mismatch in multiple sequence contexts, as we show for the identification of low-abundance mutations in samples of blood or tissue from patients with cancer. The method can be coupled with next-generation sequencing, droplet digital polymerase chain reaction, Sanger sequencing, fluorescent-probe-based assays and other mutation-detection methods.

Effect of umifenovir (arbidol) versus standard care on clinical outcome in patients with COVID-19: a retrospective cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to spread quickly throughout the world, mainly due to the lack of effective drug therapies and vaccines. The effectiveness of the antiviral drug umifenovir needs to be further clarified. METHODS: This retrospective cohort study included 1254 patients who were diagnosed with COVID-19 between February 19 and April 5, 2020 in Hubei Maternity and Child Health Hospital. They were divided into umifenovir group (n = 760, 60.60%) and control group (n = 496) without using umifenovir. The primary endpoint was a composite of intubation or death in a time-to-event analysis. The clinical outcomes were compared between the two groups using multivariable Cox analysis with inverse probability weighting according to the propensity score. RESULTS: A total of 760 (60.60%) patients received umifenovir, and 496 patients did not do so. Of the enrolled patients, 1049 (83.65%) had mild or moderate COVID-19, and the remaining 205 had severe or critical COVID-19. The mortality rate in the umifenovir group was 2.76% (21/760) versus 2.02% (10/494) in the control group. In terms of treatment outcomes, the discharge status of the patients in the umifenovir group was no better than that in the control group after propensity score matching (n = 485 in each group). In addition, the respiratory rate, a severe condition, or critical condition of the disease were the three main risk factors affecting the endpoint of death (p = 0.0028, p = 0.0009 and p < 0.0001, respectively). CONCLUSION: This retrospective cohort study showed that oral administration of umifenovir alone did not improve outcomes for patients with COVID-19.

Citation of updated and co-published Cochrane Methodology Reviews.

BACKGROUND: To evaluate the number of citations for Cochrane Methodology Reviews after they have been updated or co-published in another journal, and the effect of co-publishing the review on the co-publishing journal's impact factor (IF). METHODS: We identified all Cochrane Methodology Reviews published in the Cochrane Database of Systematic Reviews (CDSR) before 2018 and searched for co-published versions in the Web of Science Core Collection database up to 16 August 2022. The included reviews were in two cohorts: those that had been published and updated in CDSR and those that had been published in CDSR and co-published in another journal. The primary outcome measured the citation number to updated and original reviews in the first five years after publication of the updated review, and assessed the citation number of co-published and non-co-published reviews in the first five years after publication of the co-published version. The secondary outcome was the ratio of an adjusted IF and the actual IF of the co-publishing journal. RESULTS: Eight updated and six original reviews were identified for the updated cohort of reviews, and four co-published reviews were included in the co-published cohort. The original reviews continued to be cited after the update was published but the median for the total number of citations was non-significantly higher for the updated reviews than for their original version[161 (Interquartile range (IQR) 85, 198) versus 113 (IQR 15, 433)]. The median number of total citations [362 (IQR 179, 840) versus 145 (IQR 75, 445)] and the median number of citations to the review in the first five years after co-publication combined and in each of those years was higher in the co-published group than in the non-co-published group. One of the three journals that co-published Reviews in the first year and two journals in the second year had a lower IF after co-publication. CONCLUSIONS: Earlier versions of Cochrane Methodology Reviews continue to be cited after an update is published, which raises doubts about whether those citing are using the most recent evidence or are aware of the update. Co-publication facilitates broader application and dissemination of Cochrane methodology evidence.

Host Sorbitol and Bacterial Sorbitol Utilization Promote Clostridioides difficile Infection in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is a widespread gastrointestinal inflammatory disorder with globally increasing incidence. Clostridioides difficile infection (CDI) often occurs in patients with intestinal dysbiosis, such as after antibiotic therapy. Patients with IBD have increased incidence of CDI and the clinical outcome of IBD is reportedly worsened by CDI. However, the underlying reasons remain poorly understood. METHODS: We performed a retrospective single-center and a prospective multicenter analysis of CDI in patients with IBD, including genetic typing of C difficile isolates. Furthermore, we performed a CDI mouse model to analyze the role of the sorbitol metabolization locus that we found distinguished the main IBD- and non-IBD-associated sequence types (STs). Moreover, we analyzed sorbitol concentration in the feces of patients with IBD and healthy individuals. RESULTS: We detected a significant association of specific lineages with IBD, particularly increased abundance of ST54. We found that in contrast to the otherwise clinically predominant ST81, ST54 harbors a sorbitol metabolization locus and was able to metabolize sorbitol in vitro and in vivo. Notably, in the mouse model, ST54 pathogenesis was dependent on intestinal inflammation-induced conditions and the presence of sorbitol. Furthermore, we detected significantly increased sorbitol concentrations in the feces of patients with active IBD vs patients in remission or healthy controls. CONCLUSIONS: Sorbitol and sorbitol utilization in the infecting C difficile strain play major roles for the pathogenesis and epidemiology of CDI in patients with IBD. CDI in patients with IBD may thus be avoided or improved by elimination of dietary sorbitol or suppression of host-derived sorbitol production.

Strong Magnetocaloric Coupling in Oxyorthosilicate with Dense Gd3+ Spins.

Searching for working refrigerant materials is the key element in the design of magnetic cooling devices. Herein, we report on the thermodynamic and magnetocaloric parameters of an X1 phase oxyorthosilicate, Gd2SiO5, by field-dependent static magnetization and specific heat measurements. An overall correlation strength of |J|S2 ≈ 3.4 K is derived via the mean-field estimate, with antiferromagnetic correlations between the ferromagnetically coupled Gd-Gd layers. The magnetic entropy change -ΔSm is quite impressive, reaches 0.40 J K-1 cm-3 (58.5 J K-1 kg-1) at T = 2.7 K, with the largest adiabatic temperature change Tad = 23.2 K for a field change of 8.9 T. At T = 20 K, the lattice entropy SL is small enough compared to the magnetic entropy Sm, Sm/SL = 21.3, which warrants its potential in 2 -20 K cryocoolers with both the Stirling and Carnot cycles. Though with relatively large exchange interactions, the layered A-type spin arrangement ultimately enhances the magnetocaloric coupling, raising the possibilities of designing magnetic refrigerants with a high ratio of cooling capacity to volume.

A landscape of Long non-coding RNAs reveals the leading transcriptome alterations in murine aorta during aging.

Considerable studies have given convincing evidence of a forefront position for vascular aging in preventing cardiovascular disease. Various functions of Long non-coding RNAs (lncRNAs) are becoming increasingly distinct in aging-related diseases. This study aims at a better insight into the expression profile and mechanisms of lncRNAs in vascular senescence. High-throughput sequencing was used to detect the differential expression (DE) of lncRNAs and mRNAs in the aorta of 96 W and 8 W-old mice, while 1423 lncRNAs and 80 mRNAs were differentially expressed. By performing GO and KEGG enrichment analysis, we found that DE lncRNAs were mainly involved in purine metabolism and cGMP-PKG signaling pathways. In addition, a co-expression functional network of DE lncRNAs and DE mRNAs was constructed, and ENSMUST00000218874 could interact with 41 DE mRNAs, suggesting that it may play an essential role in vascular senescence. This study reveals DE lncRNAs in naturally aging vascular, which may provide new ideas and targets for aging-related cardiovascular diseases.