Miracle-dz/UniFAR-FTUs huggingface dataset:
Tyrocidine A interactions with saccharides investigated by CD and NMR spectroscopies

Tyrocidines are a family of cyclic decapeptides produced by the soil bacterium, Brevibacillus parabrevis. These antibiotic peptides can be used to prevent infections in agriculture and food industry but also to prepare antimicrobial lozenges, creams, and dressings for medical applications. It has been observed that the tyrocidines interact with saccharides such as cellulose from their soil environment, as well as sugars in culture media and glycans in fungal cell walls. Here, we investigated the interactions of tyrocidines with glucose, sucrose, and cellotetraose (as cellulose model) in a quantitative fashion utilising CD and NMR spectroscopy. The CD and NMR spectra of tyrocidine A (TrcA) were analysed as a function of solvent composition, and the spectral properties agree with the formation of oligomeric structures that are governed by β‐sheet secondary structures once the acetonitrile content of the solvent is increased. Saccharides seem to also induce TrcA spectral changes reverting those induced by organic solvents. The CD spectral changes of TrcA in the presence of glucose agree with new ordered H‐bonding, possibly β‐sheet structures. The amides involved in intramolecular H‐bonding remained largely unaffected by the environmental changes. In contrast, amides exposed to the exterior and/or involved in TrcA intermolecular association show the largest 1H chemical shift changes. CD and NMR spectroscopic investigations correlated well with TrcA‐glucose interactions characterized by a dissociation constant around 200 μM. Interestingly, the association of cellotetraose corresponds closely to the additive effect from four glucose moieties, while a much higher dissociation constant was observed for sucrose. Similar trends to TrcA for binding to the three saccharides were observed for the analogous tyrocidines, tyrocidine B, and tyrocidine C. These results therefore indicate that the tyrocidine interactions with the glucose monosaccharide unit are fairly specific and reversible.
Putting the person in person-centered care: Stakeholder experiences in pediatric traumatic brain injury.

PURPOSE This pilot study sought to describe the perspectives and experiences of survivors of pediatric traumatic brain injury (pTBI), their caregivers, and the medical professionals who serve them. METHODS Thirteen people participated in semi-structured interviews: five survivors of pTBI, their primary caregivers, and three medical professionals who work with persons who have sustained pTBI. The study involved a prospective, qualitative, participatory action research model with convenience sampling. All interviews were transcribed and thematic analysis identified central concepts within and between groups. Additionally, the Consolidated Criteria for Reporting Qualitative Research (COREG) were applied. RESULTS This study found that survivors of pTBI and their caregivers commonly noted later developing issues, social challenges, and difficulty in post-rehabilitation transitions. In addition, both caregivers and medical professionals reported the need for improved follow-up with survivors, evidence-based research, and medical and therapy providers with specific training on pTBI. CONCLUSIONS The perspectives provided by key stakeholders in this pilot study identify common themes that should be central to driving innovation in rehabilitation research and clinical care.
Indoor Nature Interventions for Health and Wellbeing of Older Adults in Residential Settings: A Systematic Review.

BACKGROUND AND OBJECTIVES Having contact with nature can be beneficial for health and wellbeing, but many older adults face barriers with getting outdoors. We conducted a systematic review of quantitative studies on health and wellbeing impacts of indoor forms of nature (both real and simulated/artificial), for older adults in residential settings. RESEARCH DESIGN AND METHODS Search terms relating to older adults and indoor nature were run in 13 scientific databases (MEDLINE, CINAHL, AgeLine, Environment Complete, AMED, PsychINFO, EMBASE, HMIC, PsychARTICLES, Global Health, Web of Knowledge, Dissertations and Theses Global, and ASSIA). We also pursued grey literature, global clinical trials registries, and a range of supplementary methods. RESULTS Of 6,131 articles screened against eligibility criteria, 26 studies were accepted into the review, and were quality-appraised using the Effective Public Health Practice Project (EPHPP) tool. The participants were 930 adults aged over 60. Nature interventions and health/wellbeing outcomes were heterogeneous, which necessitated a narrative synthesis. The evidence base was generally weak, with 18 of 26 studies having a high risk of bias. However, several higher-quality studies found indoor gardening and horticulture programs were effective for cognition, psychological wellbeing, social outcomes, and life satisfaction. DISCUSSION AND IMPLICATIONS There is inconsistent evidence that indoor nature exposures are beneficial for older care residents. We expect that successful interventions were, at least partly, facilitating social interaction, supporting feelings of autonomy/control, and promoting skill development, that is, factors not necessarily associated with nature per se. Higher-quality studies with improved reporting standards are needed to further elucidate these mechanisms.
Dennd1a, a susceptibility gene for polycystic ovary syndrome, is essential for mouse embryogenesis

The DENND1A has been identified as a guanine nucleotide exchange factor for small GTPase Rab35, which functions in endocytic trafficking to mediate the recycling of selective cargos. Genetic alterations within the DENND1A gene have been implicated in human disease such as polycystic ovary syndrome (PCOS). However, the role of DENND1A in developmental and reproductive processes is largely unknown.
Temporal trends in cognitive function of older US adults associated with population changes in demographic and cardiovascular profiles

Background Recent estimates suggest that dementia incidence is decreasing in the US possibly due to better management of cardiovascular disease (CVD) risk factors, but these studies lack repeated cross-sectional assessment among a representative US sample. Our objective was to assess temporal trends in cognitive performance in relation to CVD risk factors among older National Health and Nutrition Examination Survey (NHANES) participants. Methods We used repeated cross-sectional assessment of 5711 participants ≥60 years of age from four NHANES cycles: 1999–2000, 2001–2002, 2011–2012 and 2013–2014. Cognitive function was assessed during each cycle with the Digit Symbol Substitution Test (DSST). We estimated mean DSST score at each cycle and annual trend in DSST before and after adjustment for age, sex, race/ethnicity, education, smoking status, blood pressure, glucose status and body mass index. Results DSST scores was significantly higher for 2011–2012 (difference: 6.7, 95% CI 4.4 to 9.0) and 2013–2014 (difference: 6.2, 95% CI 4.0 to 8.5), but not 2001–2002 (difference: 2.3, 95% CI −0.01 to 4.6) as compared with 1999–2000 before adjustment. We observed a linear trend for higher annual DSST score before adjustment (DSST/year: 0.44, 95% CI 0.31 to 0.57) and after adjustment for age, sex, race/ethnicity, educational attainment and CVD risk factors (DSST/year: 0.17, 95% CI 0.08 to 0.26). Educational attainment was most strongly associated with the attenuation in the trend in cognitive function (77% of trend attenuation and 20% of variance in DSST). Conclusion Cognitive function is improving over time for US adults aged ≥60 years. These improvements are strongly associated with greater educational attainment and irrespective of the changing US demographic and cardiovascular health profiles.
Formation Mechanism of Benzo(a)pyrene: One of the Most Carcinogenic Polycyclic Aromatic Hydrocarbons (PAH)

The formation of polycyclic aromatic hydrocarbons (PAHs) is a strong global concern due to their harmful effects. To help the reduction of their emissions, a crucial understanding of their formation and a deep exploration of their growth mechanism is required. In the present work, the formation of benzo(a)pyrene was investigated computationally employing chrysene and benz(a)anthracene as starting materials. It was assumed a type of methyl addition/cyclization (MAC) was the valid growth mechanism in this case. Consequently, the reactions implied addition reactions, ring closures, hydrogen abstractions and intramolecular hydrogen shifts. These steps of the mechanism were computed to explore benzo(a)pyene formation. The corresponding energies of the chemical species were determined via hybrid density funcional theory (DFT), B3LYP/6-31+G(d,p) and M06-2X/6-311++G(d,p). Results showed that the two reaction routes had very similar trends energetically, the difference between the energy levels of the corresponding molecules was just 6.13 kJ/mol on average. The most stable structure was obtained in the benzo(a)anthracene pathway.
Intramolecular isotopic evidence for bacterial oxidation of propane in subsurface natural gas reservoirs

Significance Microorganisms can oxidize hydrocarbons anaerobically, but the detection and quantification of this process in natural settings remains difficult, impeding reliable estimation of these processes at the global scale. We have used the technique of position-specific isotope analysis of propane and show that anaerobic biological degradation of propane leads to a specific signature that differs from that of propane produced from thermal decomposition of higher hydrocarbons. When applied to natural gas reservoirs, we show that anaerobic bacterial oxidation of propane can be detected and quantified, which is not the case with the use of conventional methods. Our findings are thus of importance for the detection of subsurface biology, for the understanding of the carbon cycle, and more broadly for environmental sciences. Microbial anaerobic oxidation of hydrocarbons is a key process potentially involved in a myriad of geological and biochemical environments yet has remained notoriously difficult to identify and quantify in natural environments. We performed position-specific carbon isotope analysis of propane from cracking and incubation experiments. Anaerobic bacterial oxidation of propane leads to a pronounced and previously unidentified 13C enrichment in the central position of propane, which contrasts with the isotope signature associated with the thermogenic process. This distinctive signature allows the detection and quantification of anaerobic oxidation of hydrocarbons in diverse natural gas reservoirs and suggests that this process may be more widespread than previously thought. Position-specific isotope analysis can elucidate the fate of natural gas hydrocarbons and provide insight into a major but previously cryptic process controlling the biogeochemical cycling of globally significant greenhouse gases.
HDAC Inhibitors: Therapeutic Potential in Fibrosis-Associated Human Diseases

Fibrosis is characterized by excessive deposition of the extracellular matrix and develops because of fibroblast differentiation during the process of inflammation. Various cytokines stimulate resident fibroblasts, which differentiate into myofibroblasts. Myofibroblasts actively synthesize an excessive amount of extracellular matrix, which indicates pathologic fibrosis. Although initial fibrosis is a physiologic response, the accumulated fibrous material causes failure of normal organ function. Cardiac fibrosis interferes with proper diastole, whereas pulmonary fibrosis results in chronic hypoxia; liver cirrhosis induces portal hypertension, and overgrowth of fibroblasts in the conjunctiva is a major cause of glaucoma surgical failure. Recently, several reports have clearly demonstrated the functional relevance of certain types of histone deacetylases (HDACs) in various kinds of fibrosis and the successful alleviation of the condition in animal models using HDAC inhibitors. In this review, we discuss the therapeutic potential of HDAC inhibitors in fibrosis-associated human diseases using results obtained from animal models.
Descemet's Membrane Modulation of Posterior Corneal Fibrosis

Purpose The purpose of this study was to evaluate the effect of removal of Descemet's basement membrane and endothelium compared with removal of the endothelium alone on posterior corneal fibrosis. Methods Twelve New Zealand White rabbits were included in the study. Six eyes had removal of the Descemet's membrane–endothelial complex over the central 8 mm of the cornea. Six eyes had endothelial removal with an olive-tipped cannula over the central 8 mm of the cornea. All corneas developed stromal edema. Corneas in both groups were cryofixed in optimum cutting temperature (OCT) formula at 1 month after surgery. Immunohistochemistry (IHC) was performed for α-smooth muscle actin (SMA), keratocan, CD45, nidogen-1, vimentin, and Ki-67, and a TUNEL assay was performed to detect apoptosis. Results Six of six corneas that had Descemet's membrane–endothelial removal developed posterior stromal fibrosis populated with SMA+ myofibroblasts, whereas zero of six corneas that had endothelial removal alone developed fibrosis or SMA+ myofibroblasts (P < 0.01). Myofibroblasts in the fibrotic zone of corneas that had Descemet's membrane–endothelial removal were undergoing both mitosis and apoptosis at 1 month after surgery. A zone between keratocan+ keratocytes and SMA+ myofibroblasts contained keratocan-SMA-vimentin+ cells that were likely CD45− corneal fibroblasts and CD45+ fibrocytes. Conclusions Descemet's basement membrane has an important role in modulating posterior corneal fibrosis after injury that is analogous to the role of the epithelial basement membrane in modulating anterior corneal fibrosis after injury. Fibrotic areas had myofibroblasts undergoing mitosis and apoptosis, indicating that fibrosis is in dynamic flux.
Loss of genomic integrity induced by lysosphingolipid imbalance drives ageing in the heart

Cardiac dysfunctions dramatically increase with age. Revealing a currently unknown contributor to cardiac ageing, we report the age‐dependent, cardiac‐specific accumulation of the lysosphingolipid sphinganine (dihydrosphingosine, DHS) as an evolutionarily conserved hallmark of the aged vertebrate heart. Mechanistically, the DHS‐derivative sphinganine‐1‐phosphate (DHS1P) directly inhibits HDAC1, causing an aberrant elevation in histone acetylation and transcription levels, leading to DNA damage. Accordingly, the pharmacological interventions, preventing (i) the accumulation of DHS1P using SPHK2 inhibitors, (ii) the aberrant increase in histone acetylation using histone acetyltransferase (HAT) inhibitors, (iii) the DHS1P‐dependent increase in transcription using an RNA polymerase II inhibitor, block DHS‐induced DNA damage in human cardiomyocytes. Importantly, an increase in DHS levels in the hearts of healthy young adult mice leads to an impairment in cardiac functionality indicated by a significant reduction in left ventricular fractional shortening and ejection fraction, mimicking the functional deterioration of aged hearts. These molecular and functional defects can be partially prevented in vivo using HAT inhibitors. Together, we report an evolutionarily conserved mechanism by which increased DHS levels drive the decline in cardiac health.
Pyrite formation from FeS and H2S is mediated through microbial redox activity

Significance Pyrite is the most abundant iron−sulfur mineral in sediments. Over geological times, its burial controlled oxygen levels in the atmosphere and sulfate concentrations in seawater. However, the mechanism of pyrite formation in sediments is still being debated. We show that lithotrophic microorganisms can mediate the transformation of FeS and H2S to FeS2 at ambient temperature if metabolically coupled to methane-producing archaea. Our results provide insights into a metabolic relationship that could sustain part of the deep biosphere and lend support to the iron−sulfur-world theory that postulated FeS transformation to FeS2 as a key energy-delivering reaction for life to emerge. The exergonic reaction of FeS with H2S to form FeS2 (pyrite) and H2 was postulated to have operated as an early form of energy metabolism on primordial Earth. Since the Archean, sedimentary pyrite formation has played a major role in the global iron and sulfur cycles, with direct impact on the redox chemistry of the atmosphere. However, the mechanism of sedimentary pyrite formation is still being debated. We present microbial enrichment cultures which grew with FeS, H2S, and CO2 as their sole substrates to produce FeS2 and CH4. Cultures grew over periods of 3 to 8 mo to cell densities of up to 2 to 9 × 106 cells per mL−1. Transformation of FeS with H2S to FeS2 was followed by 57Fe Mössbauer spectroscopy and showed a clear biological temperature profile with maximum activity at 28 °C and decreasing activities toward 4 °C and 60 °C. CH4 was formed concomitantly with FeS2 and exhibited the same temperature dependence. Addition of either penicillin or 2-bromoethanesulfonate inhibited both FeS2 and CH4 production, indicating a coupling of overall pyrite formation to methanogenesis. This hypothesis was supported by a 16S rRNA gene-based phylogenetic analysis, which identified at least one archaeal and five bacterial species. The archaeon was closely related to the hydrogenotrophic methanogen Methanospirillum stamsii, while the bacteria were most closely related to sulfate-reducing Deltaproteobacteria, as well as uncultured Firmicutes and Actinobacteria. Our results show that pyrite formation can be mediated at ambient temperature through a microbially catalyzed redox process, which may serve as a model for a postulated primordial iron−sulfur world.
Emulating a trial of joint dynamic strategies: An application to monitoring and treatment of HIV‐positive individuals

Decisions about when to start or switch a therapy often depend on the frequency with which individuals are monitored or tested. For example, the optimal time to switch antiretroviral therapy depends on the frequency with which HIV‐positive individuals have HIV RNA measured. This paper describes an approach to use observational data for the comparison of joint monitoring and treatment strategies and applies the method to a clinically relevant question in HIV research: when can monitoring frequency be decreased and when should individuals switch from a first‐line treatment regimen to a new regimen?
Are We Blinded by Desire? Relationship Motivation and Sexual Risk-Taking Intentions during Condom Negotiation

Effective condom negotiation skills support better sexual health for both men and women. The current study explored relationship motivation (motivation to establish and maintain long-term romantic relationships), gender, and sexual orientation as factors influencing the condom negotiation process. Participants (177 heterosexual women, 157 heterosexual men, and 106 men who have sex with men) read a vignette describing an encounter with a hypothetical new sexual/romantic partner and responded to embedded items and scales. Stronger relationship motivation predicted increased willingness to have condomless sex among women who perceived greater familiarity with the hypothetical partner. Gender and sexual orientation predicted different preferences for condom insistence strategies. The findings suggest that there are a number of conditions that make it more difficult to recognize risk during a sexual encounter and demonstrate how the process of condom negotiation can be impacted by gender, sexual orientation, and relationship motivation.
Carbon budgets of wetland ecosystems in China

Wetlands contain a large proportion of carbon (C) in the biosphere and partly affect climate by regulating C cycles of terrestrial ecosystems. China contains Asia's largest wetlands, accounting for about 10% of the global wetland area. Although previous studies attempted to estimate C budget in China's wetlands, uncertainties remain. We conducted a synthesis to estimate C uptake and emission of wetland ecosystems in China using a dataset compiled from published literature. The dataset comprised 193 studies, including 370 sites representing coastal, river, lake and marsh wetlands across China. In addition, C stocks of different wetlands in China were estimated using unbiased data from the China Second Wetlands Survey. The results showed that China's wetlands sequestered 16.87 Pg C (315.76 Mg C/ha), accounting for about 3.8% of C stocks in global wetlands. Net ecosystem productivity, jointly determined by gross primary productivity and ecosystem respiration, exhibited annual C sequestration of 120.23 Tg C. China's wetlands had a total gaseous C loss of 173.20 Tg C per year from soils, including 154.26 Tg CO2‐C and 18.94 Tg CH4‐C emissions. Moreover, C stocks, uptakes and gaseous losses varied with wetland types, and were affected by geographic location and climatic factors (precipitation and temperature). Our results provide better estimation of the C budget in China's wetlands and improve understanding of their contribution to the global C cycle in the context of global climate change.
Directed Differentiation of Pluripotent Stem Cells by Transcription Factors

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been used as promising tools for regenerative medicine, disease modeling, and drug screening. Traditional and common strategies for pluripotent stem cell (PSC) differentiation toward disease-relevant cell types depend on sequential treatment of signaling molecules identified based on knowledge of developmental biology. However, these strategies suffer from low purity, inefficiency, and time-consuming culture conditions. A growing body of recent research has shown efficient cell fate reprogramming by forced expression of single or multiple transcription factors. Here, we review transcription factor-directed differentiation methods of PSCs toward neural, muscle, liver, and pancreatic endocrine cells. Potential applications and limitations are also discussed in order to establish future directions of this technique for therapeutic purposes.
Serum cholesterol positively associated with oxidative DNA damage: a propensity score-matched analysis

Abstract Oxidative DNA damage pathogenically links to some major diseases. This study aimed to comprehensively assess the association between serum total cholesterol (TC) and oxidative DNA damage based on propensity score matching (PSM) method. A total of 407 participants chronically exposed to arsenic via drinking water from China were enrolled. Oxidative DNA damage was determined with urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG). Serum TC was classified into favourable TC (FTC, TC <5.18 mmol/L) and unfavourable TC (NFTC, TC ≥5.18 mmol/L) categories. Multivariable generalised linear regression model was applied to examine the association. Of 407 participants, 125 pairs with FTC and NFTC subjects were matched using PSM. Urinary 8-OHdG/creatinine levels in NFTC were significantly higher than those in FTC category (p = .002). As compared to the counterparts, additional adjusted log-transformed 8-OHdG/creatinine increase was observed in NFTC for unmatched (β = 0.12, p = .052) and matched (β = 0.17, p < .001) participants, respectively. We also detected obviously increased log-transformed urinary 8-OHdG/creatinine with per interquartile range raise of serum TC either in unmatched (β = 0.10, p = .007) or matched (β = 0.16, p = .003) subjects. In conclusion, serum TC was independently associated with oxidative DNA damage. Our findings provided new insights on the health promotion of lipids relevant to the early warning of diseases due to oxidative DNA damage.