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Abstract Signaling systems of microorganisms are responsible for regulating the physiological and metabolic processes and also play vital roles in the communications of cells. Identifying signaling molecules mediating the cross-talks is challenging yet highly desirable for comprehending the microbial interactions. Here, we demonstrate that a pathogenic Gram-negative Chromobacterium violaceum exerts significant influence on the morphological differentiation and secondary metabolism of Gram-positive Streptomyces. The physiological metabolisms are directly modulated by three novel cinnamoyl lipids (CVCL1, 2, and 3) from C. violaceum CV12472, whose biosynthesis is under the control of N-acylhomoserine lactone signaling system. Furthermore, a receptor of CVCLs in Streptomyces ansochromogenes 7100 is determined to be SabR1, the cognate receptor of γ-butenolide signaling molecules. This study reveals an unprecedented mode of microbial interactions, and the quorum sensing signaling systems in these two groups of bacteria can be bridged via CVCLs, suggesting that CVCLs can modulate the physiological metabolism of cross-phylum microorganisms.

Abstract Currently, there is still debate over the effectiveness of transcranial direct current stimulation (tDCS) in treating obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD) and anxiety disorders (ADs). To investigate the immediate and long-term effectiveness of tDCS in these diseases, we conducted a systematic review and quantitative analysis of existing literature on the treatment of OCD, PTSD, and ADs with tDCS. Following the PRISMA guidelines, we searched seven electronic databases and systematically retrieved articles published from May 2012 to June 2024 that compared the effects of active tDCS with sham stimulation in the treatment of these disorders. We included primary outcome measures such as the change scores in disorder-specific and general anxiety symptoms before and after treatment, as well as secondary outcomes such as changes in disorder-specific and general anxiety symptoms at follow-up. We also assessed the impact of tDCS on depressive symptoms. Fifteen papers met the eligibility criteria. Overall, the results of meta-analysis indicated that tDCS had a high effect in improving specific symptoms (SMD = −0.73, 95% CI: −1.09 to −0.37) and general anxiety symptoms (SMD = −0.75; 95% CI: −1.23 to −0.26) in OCD, PTSD and ADs, with effects lasting up to 1 month and showing a moderate effect size. Furthermore, tDCS demonstrated immediate and significant alleviation of depressive symptoms in these diseases. This study concludes that tDCS can serve as a non-invasive brain stimulation technology for treating these disorders, and the therapeutic effects can be maintained for a period of time.

Abstract Background Microbial genome sequencing and analysis revealed the presence of abundant silent secondary metabolites biosynthetic gene clusters (BGCs) in streptomycetes. Activating these BGCs has great significance for discovering new compounds and novel biosynthetic pathways. Results In this study, we found that ovmZ and ovmW homologs, a pair of interdependent transcriptional regulators coding genes, are widespread in actinobacteria and closely associated with the biosynthesis of secondary metabolites. Through co-overexpression of native ovmZ and ovmW in Streptomyces neyagawaensis NRRL B-3092, a silent type II polyketide synthase (PKS) gene cluster was activated to produce gephyromycin A, tetrangomycin and fridamycin E with the yields of 22.3 ± 8.0 mg/L, 4.8 ± 0.5 mg/L and 20.3 ± 4.1 mg/L respectively in the recombinant strain of S.ne/pZnWn. However, expression of either ovmZ or ovmW failed to activate this gene cluster. Interestingly, overexpression of the heterologous ovmZ and ovmW pair from oviedomycin BGC of S. ansochromogenes 7100 also led to awakening of this silent angucyclinone BGC in S. neyagawaensis. Conclusion A silent angucyclinone BGC was activated by overexpressing both ovmZ and ovmW in S. neyagawaensis. Due to the wide distribution of ovmZ and ovmW in the BGCs of actinobacteria, co-overexpression of ovmZ and ovmW could be a strategy for activating silent BGCs, thus stimulating the biosynthesis of secondary metabolites.

Abstract Background It remains unknown how the patterns of change of social isolation and loneliness are associated with the onset of cardiovascular disease (CVD) and mortality. We aimed to investigate the longitudinal association of changes in social isolation and loneliness with incident CVD, all-cause mortality, CVD mortality and subsequent cardiac function. Methods This prospective cohort study included 18,258 participants aged 38–73 years who participated in visit 0 (2006–2010) and visit 1 (2012–2013) using UK Biobank (mean age 57.1, standard deviation [SD] 7.4; 48.7% males). Social isolation or loneliness was categorized into four patterns: never, transient, incident, and persistent. Incident CVD, all-cause and CVD mortality were ascertained through linkage data. Cardiac function was assessed by cardiovascular magnetic resonance imaging in a subsample (N = 5188; visit 2, since 2014). Results Over a median follow-up of 8.3 (interquartile range [IQR] 8.1–8.6) years, compared with never social isolation, persistent social isolation was associated with the higher risk of incident CVD (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.03–1.33), all-cause (1.42, 1.12–1.81) and CVD (1.53, 1.05–2.23) mortality. Likewise, persistent loneliness was strongly associated with the greater risk of incident CVD (1.13, 1.00–1.27), all-cause (1.28, 1.02–1.61) and CVD mortality (1.52, 1.06–2.18). Conclusions Persistent social isolation and loneliness posed a substantially higher risk for incident CVD, all-cause and CVD mortality, and cardiac dysfunction than other patterns. Persistent social isolation and loneliness, along with an increasing cumulative score, are associated with lower cardiac function. Graphical Abstract

Abstract. Background:. Prenatal and postnatal factors may have joint effects on cardiovascular health, and we aimed to assess the joint association of birth weight and ideal cardiovascular health metrics (ICVHMs) prospectively in adulthood with incident cardiovascular disease (CVD). Methods:. In the UK Biobank, 227,833 participants with data on ICVHM components and birth weight and without CVD at baseline were included. The ICVHMs included smoking, body mass index, physical activity, diet information, total cholesterol, blood pressure, and hemoglobin A1c. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women. Results:. Over a median follow-up period of 13.0 years (2,831,236 person-years), we documented 17,477 patients with incident CVD. Compared with participants with birth weights of 2.5–4.0 kg, the HRs (95% CIs) of CVD among those with low birth weights was 1.08 (1.00–1.16) in men and 1.23 (1.16–1.31) in women. The association between having a birth weight

Background & Aims: The EAT-Lancet Commission in 2019 advocated a plant-centric diet for health and environmental benefits, but its relation to metabolic dysfunction-associated steatotic liver disease (MASLD) is unclear. We aimed to discover the metabolite profile linked to the EAT-Lancet diet and its association with MASLD risk, considering genetic predisposition. Methods: We analyzed data from 105,752 UK Biobank participants with detailed dietary and metabolomic information. We constructed an EAT-Lancet diet index and derived a corresponding metabolomic signature through elastic net regression. A weighted polygenic risk score for MASLD was computed from associated risk variants. The Cox proportional hazards model was employed to estimate hazard ratios (HRs) and 95% CIs for the risk of MASLD (defined as hospital admission or death). Results: During a median follow-up period of 11.6 years, 1,138 cases of MASLD were documented. Participants in the highest group for the EAT-Lancet diet index had a multivariable HR of 0.79 (95% CI 0.66–0.95) for MASLD compared to the lowest group. The diet's impact was unaffected by genetic predisposition to MASLD (p = 0.42). Moreover, a robust correlation was found between the metabolomic signature and the EAT-Lancet diet index (Pearson r = 0.29; p

Abstract Background Insomnia and eveningness are common and often comorbid conditions in youths. While cognitive behavioural therapy for insomnia (CBT-I) has been suggested as a promising intervention, it remains unclear whether it is sufficient to also address circadian issues in youths. In addition, despite that light has been shown to be effective in phase-shifting one’s circadian rhythm, there has been limited data on the effects of bright light therapy and its combination with CBT-I on sleep and circadian outcomes in youths. The current protocol outlines a randomised controlled trial that examines the efficacy of CBT-I and CBT-I plus bright light therapy (BLT) in reducing insomnia severity, improving mood symptoms and daytime functioning (e.g. sleepiness, fatigue, cognitive function), and improving subjective and objective sleep and circadian measures compared to a waitlist control group. Methods We will carry out a randomised controlled trial (RCT) with 150 youths aged 12–24 who meet the criteria of insomnia and eveningness. Participants will be randomised into one of three groups: CBT-I with bright light therapy, CBT-I with placebo light, and waitlist control. Six sessions of CBT-I will be delivered in a group format, while participants will be currently asked to use a portable light device for 30 min daily immediately after awakening throughout the intervention period for bright light therapy. The CBT-I with light therapy group will receive bright constant green light (506 lx) while the CBT-I with placebo light group will receive the modified light device with the LEDs emitting less than 10 lx. All participants will be assessed at baseline and post-treatment, while the two active treatment groups will be additionally followed up at 1 month and 6 months post-intervention. The primary outcome will be insomnia severity, as measured by the Insomnia Severity Index. Secondary outcomes include self-reported mood, circadian, daytime functioning, and quality of life measures, as well as sleep parameters derived from actigraphy and sleep diary and neurocognitive assessments. Objective measures of the circadian phase using dim-light melatonin onset assessment and sleep parameters using polysomnography will also be included as the secondary outcomes. Discussion This study will be the first RCT to directly compare the effects of CBT-I and BLT in youths with insomnia and eveningness. Findings from the study will provide evidence to inform the clinical management of insomnia problems and eveningness in youths. Trial registration ClinicalTrials.gov NCT04256915. Registered on 5 February 2020.

Purpose: The aim of the current study was to investigate the association of accelerometer-measured sleep duration and different intensities of physical activity (PA) with the risk of incident type 2 diabetes in a population-based prospective cohort study. Methods: Altogether, 88,000 participants (mean age = 62.2 ± 7.9 years, mean ± SD) were included from the UK Biobank. Sleep duration (short: 8 h/day) and PA of different intensities were measured using a wrist-worn accelerometer over a 7-day period between 2013 and 2015. PA was classified according to the median or World Health Organization-recommendation: total volume of PA (high, low), moderate-to-vigorous PA (MVPA) (recommended, not recommended), and light-intensity PA (high, low). Incidence of type 2 diabetes was ascertained using hospital records or death registries. Results: During a median follow-up of 7.0 years, 1615 incident type 2 diabetes cases were documented. Compared with normal sleep duration, short (hazard ratio (HR) = 1.21, 95% confidence interval (95%CI): 1.03–1.41) but not long sleep duration (HR = 1.01, 95%CI: 0.89–1.15) was associated with excessive type 2 diabetes risk. This increased risk among short sleepers seems to be protected against by PA. Compared with normal sleepers with high or recommended PA, short sleepers with low volume of PA (HR = 1.81, 95%CI: 1.46–2.25), not recommended (below the World Health Organization-recommended level of) MVPA (HR = 1.92, 95%CI: 1.55–2.36), or low light-intensity PA (HR = 1.49, 95%CI: 1.13–1.90) had a higher risk of type 2 diabetes, while short sleepers with a high volume of PA (HR = 1.14, 95%CI: 0.88–1.49), recommended MVPA (HR = 1.02, 95%CI: 0.71–1.48), or high light-intensity PA (HR = 1.14, 95%CI: 0.92–1.41) did not. Conclusion: Accelerometer-measured short but not long sleep duration was associated with a higher risk of incident type 2 diabetes. A higher level of PA, regardless of intensity, potentially ameliorates this excessive risk.

AbstractErasmia pulchella has brightly colored wings and releases toxic cyanide as a defense against predation. At present, the molecular phylogenetic status of this species is still unclear. Here, we presented the first complete mitochondrial genome of the genus Erasmia, which was assembled from data generated using a genome skimming method. The assembled mitogenome was 15,197 bp in length and consists of 37 genes, including 13 protein-coding genes, two rRNAs, 22 tRNAs, and a control region. Phylogenetic analysis based on both maximum likelihood (ML) and Bayesian inference (BI) revealed that E. pulchella was most closely related to Amesia sanguiflua.

C9H8N8O8, monoclinic, P21/c (no. 14), a = 12.0387(3) Å, b = 10.7899(2) Å, c = 11.4310(3) Å, β = 111.536(3)°, V = 1,381.18(6) Å3, Z = 4, Rgt(F) = 0.0499, wRref(F2) = 0.1396, T = 293 K.

Background: Emerging evidence has linked childhood maltreatment with cardiovascular disease risk; however, the association between childhood maltreatment and cardiac arrhythmias remains unclear. Moreover, any genetic predispositions to atrial fibrillation (AF), a common cardiac arrhythmia associated with an elevated risk of stroke, heart failure, and mortality, that modify such associations have been undocumented.Purpose: To examine the associations between childhood maltreatment and incident arrhythmias, and whether a genetic predisposition to arrhythmias modifies these associations.Methods: This prospective analysis included 151,741 participants from the UK Biobank (mean age 55.8 years, 43.4% male). Childhood maltreatment, including five types, was measured using the Childhood Trauma Screener (CTS). Incident arrhythmias (AF, ventricular arrhythmias [VA], and bradyarrhythmia [BA]) were documented through linked hospital admission and death registry. Weighted AF genetic risk score was calculated. Cox proportional hazard models were conducted to test for associations between childhood maltreatment and incident arrhythmias.Results: During a median follow-up of 12.21 years (interquartile range, 11.49–12.90 years), 6,588 AF, 2,093 BA, and 742 VA events occurred. Compared with the absence of childhood maltreatment, having 3–5 types of childhood maltreatment was associated with an increased risk of incident AF (HR, 1.23; 95%CI 1.09–1.37), VA (HR, 1.39; 95%CI 1.03–1.89), and BA (HR, 1.32; 95%CI 1.09–1.61) after adjusting demographic, socioeconomic and lifestyle factors. The associations between cumulative type of childhood maltreatment and the risk of AF (Poverall

Drought stress has a significant impact on the quality and quantity of lake water. Understanding this impact is crucial for preventing water security risks and pollution recovery. However, there is a lack of systemic understanding of how drought affects water quality and quantity, and how they change in multiple dimensions. This manuscript established a synthesized methodology with the principles to judge the applicability and three steps of application to detect the change in water quality and water level under severe drought in Xingyun Lake, China. Results show that (1) The water level and water quality of Xingyun Lake have a synchronous and evident response to drought during 2009–2014. The rainfall during 2008–2015 declined by 22.9 % to normal, and the inundated area and lake water depth in 2012 decreased by 10.50 % from 2002 to 1.38 m to the average depth, respectively. The pollution index climbed above 1.21 after 2008, fluctuating around 1.42. (2) Under drought, the water quality indicators significantly changed in the terms of the overall feature, trend, eigenvalue, and morphological characteristics. The water quality indicators of Set2008-2015 are significantly different from set2000-2007 and not in the groups of set1994-2000. The morphological characteristics of water quality indicators in set2008-2015 differs significantly from that in set2000-2007 shown by the minimum, maximum, median, quartiles, and extreme values. (3) Although NH3–N showed no significant change, the water quality deteriorated in the physical, chemical, and biological aspects. The TP, IMN, and BOD5 changed more evidently than DO and NH3–N. (4) Water quality grade and indicator concentration deteriorated significantly and sharply under severe drought and are threatened deeply by TP and TN. The synthesized methodology is scientifically constructed and canbe employed in the characteristics cognition of water quality and water level to severe drought in and out of this research. And the intervention time and various regulating measures for pollution degradation and water quality recovery canbe constructed based on the multi-dimensional analysis of water quality change under drought evolution.

Background Understanding the evolution of circadian rhythm dysfunction and psychopathology in the high-risk population has important implications for the prevention of bipolar disorder. Nevertheless, some of the previous studies on the emergence of psychopathologies and circadian dysfunction among high-risk populations were inconsistent and limited.Aims To examine the prevalence rates of sleep and circadian dysfunctions, mental disorders and their symptoms in the offspring of parents with (O-BD) and without bipolar disorder (O-control).Methods The study included 191 O-BD and 202 O-control subjects aged 6–21 years from the Greater Bay Area, China. The diagnoses and symptoms of sleep/circadian rhythm and mental disorders were assessed by the Diagnostic Interview for Sleep Patterns and Disorders, and the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version, respectively. Generalised estimating equations and shared frailty proportional hazards models of survival analysis were applied to compare the outcomes in the offspring.Results Adjusting for age, sex and region of recruitment, there was a significantly higher risk of delayed sleep phase symptoms (9.55% vs 2.58%, adjusted OR: 4.04) in O-BD than in O-control. O-BD had a nearly fivefold higher risk of mood disorders (11.70% vs 3.47%, adjusted OR: 4.68) and social anxiety (6.28% vs 1.49%, adjusted OR: 4.70), a fourfold higher risk of depressive disorders (11.17% vs 3.47%, adjusted OR: 3.99) and a threefold higher risk of mood symptoms (20.74% vs 10.40%, adjusted OR: 2.59) than O-control. Subgroup analysis revealed that O-BD children (aged under 12 years) had a nearly 2-fold higher risk of any mental and behavioural symptoms than O-control, while there was a nearly 4-fold higher risk of delayed sleep phase symptoms, a 7.5-fold higher risk of social anxiety and a 3-fold higher risk of mood symptoms in O-BD adolescents (aged 12 years and over).Conclusions There was an increase in delayed sleep phase symptoms in O-BD adolescents compared with their control counterparts, confirming the central role of circadian rhythm dysfunction in bipolar disorder. The findings of the specific age-related and stage-related developmental patterns of psychopathologies and circadian dysfunction in children and adolescent offspring of parents with bipolar disorder paved the way to develop specific and early clinical intervention and prevention strategies.Trial registration number NCT03656302.

Streptomycetes possess numerous gene clusters and the potential to produce a large amount of natural products. Histone deacetylase (HDAC) inhibitors play an important role in the regulation of histone modifications in fungi, but their roles in prokaryotes remain poorly understood. Here, we investigated the global effects of the HDAC inhibitor, sodium butyrate (SB), on marine-derived Streptomyces olivaceus FXJ 8.021, particularly focusing on the activation of secondary metabolite biosynthesis. The antiSMASH analysis revealed 33 secondary metabolite biosynthetic gene clusters (BGCs) in strain FXJ 8.021, among which the silent lobophorin BGC was activated by SB. Transcriptomic data showed that the expression of genes involved in lobophorin biosynthesis (ge00097–ge00139) and CoA-ester formation (e.g., ge02824), as well as the glycolysis/gluconeogenesis pathway (e.g., ge01661), was significantly up-regulated in the presence of SB. Intracellular CoA-ester analysis confirmed that SB triggered the biosynthesis of CoA-ester, thereby increasing the precursor supply for lobophorin biosynthesis. Further acetylomic analysis revealed that the acetylation levels on 218 sites of 190 proteins were up-regulated and those on 411 sites of 310 proteins were down-regulated. These acetylated proteins were particularly enriched in transcriptional and translational machinery components (e.g., elongation factor GE04399), and their correlations with the proteins involved in lobophorin biosynthesis were established by protein–protein interaction network analysis, suggesting that SB might function via a complex hierarchical regulation to activate the expression of lobophorin BGC. These findings provide solid evidence that acetylated proteins triggered by SB could affect the expression of genes involved in the biosynthesis of primary and secondary metabolites in prokaryotes.

Abstract Background Uridyl peptide compounds are renowned as a subclass of nucleoside antibiotics for their highly specific antibacterial activity against Gram-negative bacteria and the unique target of action. We previously activated the biosynthetic gene cluster of a uridyl peptide antibiotic, mureidomycin, in Streptomyces roseosporus NRRL 15998 by introducing an exogenous positive regulator gene ssaA, and the generated strain was designated as Sr-hA. This study aims to further explore mureidomycin analogs from Sr-hA as well as the collaborative roles of two wide-spread genes, SSGG-02980 and SSGG-03002 encoding putative nuclease/phosphatase and oxidoreductase respectively, in mureidomycin diversification. Results In order to understand how SSGG-02980 and SSGG-03002 contribute to mureidomycin biosynthesis, the gene disruption mutants and complementary strains were constructed. Mass spectrometry analyses revealed that two series of pairwise mureidomycin analogs were synthesized in Sr-hA with a two-dalton difference in molecular weight for each pair. By disruption of SSGG-03002, only mureidomycins with lower molecular weight (MRDs, 1–6) could be specifically accumulated in the mutant (∆03002-hA), whereas the other series of products with molecular weight plus 2 Da (rMRDs, 1ʹ–6ʹ) became dominant in SSGG-02980 disruption mutant (∆02980-hA). Further comprehensive NMR analyses were performed to elucidate the structures, and three MRDs (3, 4, 5) with unsaturated double bond at C5-C6 of uracil group were characterized from ∆03002-hA. In contrast, the paired rMRDs analogs (3ʹ, 4ʹ, 5ʹ) from ∆SSGG-02980 corresponding to 3, 4 and 5 were shown to contain a single bond at this position. The results verified that SSGG-03002 participates in the reduction of uracil ring, whereas SSGG-02980 antagonizes the effect of SSGG-03002, which has been rarely recognized for a phosphatase. Conclusions Overall, this study revealed the key roles of two wide-spread families of enzymes in Streptomyces. Of them, oxidoreductase, SSGG-03002, is involved in dihydro-mureidomycin biosynthesis of S. roseosporus, whereas nuclease/phosphatase, SSGG-02980, has an adverse effect on SSGG-03002. This kind of unusual regulation model between nuclease/phosphatase and oxidoreductase is unprecedented, providing new insights into the biosynthesis of mureidomycins in Streptomyces. The findings would be of significance for structural diversification of more uridyl peptide antibiotics against Gram-negative bacteria.

This research presents a novel current loop control strategy for a three-phase PWM rectifier system aimed at mitigating challenges related to substandard power quality, excessive current harmonics, and insufficient robustness. The suggested approach combines an extended state observer (ESO) with dual-power sliding mode control that is further enhanced by fractional-order micro-integral operators. This amalgamation enhances the adaptability of the controller to system dynamics and augments the flexibility of the current loop control mechanism. The results of this integration include diminished system oscillations, heightened immunity to external disturbances, and improved robustness and dynamics of the overall system. Through MATLAB/Simulink simulations, the effectiveness of the proposed control methodology is validated, demonstrating superior performance in terms of robustness, dynamic response, power quality enhancement, and mitigation of current harmonics when compared to conventional PI control and standard fractional-order dual-power sliding mode control techniques.

Many ectotherms hibernate to increase their chances of survival during harsh winter conditions. The role of DNA methylation in regulating gene expression related to hibernation in ectotherms remains unclear. Here, we employed whole-genome bisulfite sequencing (WGBS) technology to construct a comprehensive genome-wide DNA methylation landscape of the hindlimb muscles in the Chinese alligator during hibernation and active periods. The results indicated that methylation modifications were most abundant at CG sites, identifying 9447 differentially methylated regions (DMRs) and 2329 differentially methylated genes (DMGs). KEGG pathway enrichment analysis of the DMGs revealed significant enrichment in major pathways such as the neurotrophin signaling pathway, the MAPK signaling pathway, the GnRH signaling pathway, the biosynthesis of amino acids, and the regulation of the actin cytoskeleton, which are closely related to lipid metabolism, energy metabolism, and amino acid metabolism. Among these, 412 differentially methylated genes were located in promoter regions, including genes related to energy metabolism such as ATP5F1C, ATP5MD, PDK3, ANGPTL1, and ANGPTL2, and genes related to ubiquitin-proteasome degradation such as FBXO28, FBXO43, KLHL40, and PSMD5. These findings suggest that methylation in promoter regions may play a significant role in regulating the adaptive hibernation mechanisms in the Chinese alligator. This study contributes to a further understanding of the epigenetic mechanisms behind the hibernation of the Chinese alligator.

Background: Whether or not there is targeted pharmacotherapy for dementia, an active and healthy lifestyle that includes physical activity (PA) may be a better option than medication for preventing dementia. We examined the association between leisure-time sedentary behavior (SB) and the risk of dementia incidence and mortality. We further quantified the effect on dementia risk of replacing sedentary time with an equal amount of time spent on different physical activities. Methods: In the UK Biobank, 484,169 participants (mean age = 56.5 years; 45.2% men) free of dementia were followed from baseline (2006–2010) through July 30, 2021. A standard questionnaire measured individual leisure-time SB (watching TV, computer use, and driving) and PA (walking for pleasure, light and heavy do-it-yourself activity, strenuous sports, and other exercise) frequency and duration in the 4 weeks prior to evaluation. Apolipoprotein E (APOE) genotype data were available for a subset of 397,519 (82.1%) individuals. A Cox proportional hazard model and an isotemporal substitution model were used in this study. Results: During a median 12.4 years of follow-up, 6904 all-cause dementia cases and 2115 deaths from dementia were recorded. In comparison to participants with leisure-time SB 8 h/day, and the HR of dementia mortality was 1.35 (1.12–1.61) for >8 h/day. A 1 standard deviation increment of sedentary time (2.33 h/day) was strongly associated with a higher incidence of dementia and mortality (HR = 1.06, 95%CI: 1.03–1.08 and HR = 1.07, 95%CI: 1.03–1.12, respectively). The association between sedentary time and the risk of developing dementia was more profound in subjects 8 h/day, p for interaction = 0.013). Replacing 30 min/day of leisure sedentary time with an equal time spent in total PA was associated with a 6% decreased risk and 9% decreased mortality from dementia, with exercise (e.g., swimming, cycling, aerobics, bowling) showing the strongest benefit (HR = 0.82, 95%CI: 0.78–0.86 and HR = 0.79, 95%CI: 0.72–0.86). Compared with APOE ε4 noncarriers, APOE ε4 carriers are more likely to see a decrease in Alzheimer's disease incidence and mortality when PA is substituted for SB. Conclusion: Leisure-time SB was positively associated with the risk of dementia incidence and mortality. Replacing sedentary time with equal time spent doing PA may be associated with a significant reduction in dementia incidence and mortality risk.

Abstract The microbiota-gut-brain axis has been suggested to play an important role in Parkinson’s disease (PD). Here we performed a cross-sectional study to profile gut microbiota across early PD, REM sleep behavior disorder (RBD), first-degree relatives of RBD (RBD-FDR), and healthy controls, which could reflect the gut-brain staging model of PD. We show gut microbiota compositions are significantly altered in early PD and RBD compared with control and RBD-FDR. Depletion of butyrate-producing bacteria and enrichment of pro-inflammatory Collinsella have already emerged in RBD and RBD-FDR after controlling potential confounders including antidepressants, osmotic laxatives, and bowel movement frequency. Random forest modelling identifies 12 microbial markers that are effective to distinguish RBD from control. These findings suggest that PD-like gut dysbiosis occurs at the prodromal stages of PD when RBD develops and starts to emerge in the younger RBD-FDR subjects. The study will have etiological and diagnostic implications.

Background: The cervical anterior transpedicular screw (ATPS) fixation technology can provide adequate stability for cervical three-column injuries. However, its high risk of screw insertion and technical complexity have restricted its widespread clinical application. As an improvement over the ATPS technology, the cervical anterior transpedicular root screw (ATPRS) technology has been introduced to reduce the risk associated with screw insertion. This study aims to use finite element analysis (FEA) to investigate the biomechanical characteristics of a cervical spine model after using the novel ATPRS intervertebral fusion system, providing insights into its application and potential refinement.Methods: A finite element (FE) model of the C3-C7 lower cervical spine was established and validated. After two-level (C4-C6) anterior cervical discectomy and fusion (ACDF) surgery, FE models were constructed for the anterior cervical locked-plate (ACLP) internal fixation, the ATPS internal fixation, and the novel ATPRS intervertebral fusion system. These models were subjected to 75N axial force and 1.0 Nm to induce various movements. The range of motion (ROM) of the surgical segments (C4-C6), maximum stress on the internal fixation systems, and maximum stress on the adjacent intervertebral discs were tested and recorded.Results: All three internal fixation methods effectively reduced the ROM of the surgical segments. The ATPRS model demonstrated the smallest ROM during flexion, extension, and rotation, but a slightly larger ROM during lateral bending. Additionally, the maximum bone-screw interface stresses for the ATPRS model during flexion, extension, lateral bending, and axial rotation were 32.69, 64.24, 44.07, 35.89 MPa, which were lower than those of the ACLP and ATPS models. Similarly, the maximum stresses on the adjacent intervertebral discs in the ATPRS model during flexion, extension, lateral bending, and axial rotation consistently remained lower than those in the ACLP and ATPS models. However, the maximum stresses on the cage and the upper endplate of the ATPRS model were generally higher.Conclusion: Although the novel ATPRS intervertebral fusion system generally had greater endplate stress than ACLP and ATPS, it can better stabilize cervical three-column injuries and might reduce the occurrence of adjacent segment degeneration (ASD). Furthermore, further studies and improvements are necessary for the ATPRS intervertebral fusion system.

Background Individuals with type 2 diabetes mellitus (T2DM) are more vulnerable to social disconnection compared with the general population; however, there are few relevant studies investigating this issue.Aims To investigate whether social isolation or loneliness may be associated with subsequent risk of developing major adverse cardiovascular events, whether these associations vary according to fatal and non-fatal outcomes and how behavioural, psychological and physiological factors mediate these associations.Methods This longitudinal analysis included data from 19 360 individuals with T2DM at baseline (2006–2010) from the UK Biobank. Social isolation and loneliness were measured using self-report questionnaires. The study outcomes included the first events of myocardial infarction (MI) or stroke (n=2273) and all-cause (n=2820) or cardiovascular disease-related mortality through linked hospital data or death registries.Results Over a median follow-up of 12.4 years (interquartile range (IQR): 11.6–13.3 years), participants who were more socially isolated (most social isolation vs least social isolation) experienced increased risks for all-cause (hazard ratio (HR) : 1.33, 95% confidence interval (CI): 1.19 to 1.47) and cardiovascular disease (HR: 1.36, 95% CI: 1.17 to 1.59) mortality but not first MI or stroke. Loneliness (yes vs no) was associated with a greater risk for a composite of incident MI or stroke (HR: 1.37, 95% CI: 1.19 to 1.57) but not mortality. Social isolation was associated with fatal MI and stroke, whereas loneliness was associated with non-fatal MI and stroke. The significant associations of social isolation and loneliness with outcomes were mainly mediated by behavioural factors (mediating proportion: 17.8%–28.2% and 17.6%–17.8%, respectively).Conclusions Among individuals with T2DM, social isolation and loneliness are associated with a greater risk of developing major adverse cardiovascular events, with differences in both risks stratified according to fatal and non-fatal events and underlying mediating factors.

Abstract BackgroundAssessing patients’ suicide risk is challenging, especially among those who deny suicidal ideation. Primary care providers have poor agreement in screening suicide risk. Patients’ speech may provide more objective, language-based clues about their underlying suicidal ideation. Text analysis to detect suicide risk in depression is lacking in the literature. ObjectiveThis study aimed to determine whether suicidal ideation can be detected via language features in clinical interviews for depression using natural language processing (NLP) and machine learning (ML). MethodsThis cross-sectional study recruited 305 participants between October 2020 and May 2022 (mean age 53.0, SD 11.77 years; female: n=176, 57%), of which 197 had lifetime depression and 108 were healthy. This study was part of ongoing research on characterizing depression with a case-control design. In this study, 236 participants were nonsuicidal, while 56 and 13 had low and high suicide risks, respectively. The structured interview guide for the Hamilton Depression Rating Scale (HAMD) was adopted to assess suicide risk and depression severity. Suicide risk was clinician rated based on a suicide-related question (H11). The interviews were transcribed and the words in participants’ verbal responses were translated into psychologically meaningful categories using Linguistic Inquiry and Word Count (LIWC). ResultsOrdinal logistic regression revealed significant suicide-related language features in participants’ responses to the HAMD questions. Increased use of anger words when talking about work and activities posed the highest suicide risk (odds ratio [OR] 2.91, 95% CI 1.22-8.55; PPPP ConclusionsThis study examined the perspective of using NLP and ML to analyze the texts from clinical interviews for suicidality detection, which has the potential to provide more accurate and specific markers for suicidal ideation detection. The findings may pave the way for developing high-performance assessment of suicide risk for automated detection, including online chatbot-based interviews for universal screening.

Abstract Evidence suggests potential links between circadian rhythm and atrial fibrillation (AF). However, whether circadian disruption can predict the onset of AF in the general population remains largely unknown. We aim to investigate the association of accelerometer-measured circadian rest-activity rhythm (CRAR, the most prominent circadian rhythm in humans) with the risk of AF, and examine joint associations and potential interactions of CRAR and genetic susceptibility with AF incidence. We include 62,927 white British participants of UK Biobank without AF at baseline. CRAR characteristics, including amplitude (strength), acrophase (timing of peak activity), pseudo-F (robustness), and mesor (height), are derived by applying an extended cosine model. Genetic risk is assessed with polygenic risk scores. The outcome is the incidence of AF. During a median follow-up of 6.16 years, 1920 participants developed AF. Low amplitude [hazard ratio (HR): 1.41, 95% confidence interval (CI): 1.25–1.58], delayed acrophase (HR: 1.24, 95% CI: 1.10–1.39), and low mesor (HR: 1.36, 95% CI: 1.21–1.52), but not low pseudo-F, are significantly associated with a higher risk of AF. No significant interactions between CRAR characteristics and genetic risk are observed. Joint association analyses reveal that participants with unfavourable CRAR characteristics and high genetic risk yield the highest risk of incident AF. These associations are robust after controlling for multiple testing and in a series of sensitivity analyses. Accelerometer-measured CRAR abnormalities, characterized by decreased strength and height, and later timing of peak activity of circadian rhythm, are associated with a higher risk of AF in the general population.

There is a growing interest in the role of timing of physical activity (PA) in improving health. Here, using a large-scale cohort study, the authors show that moderate-to-vigorous PA at the optimal time of day robustly predicts lower mortality risk and may maximize the beneficial effect of PA.

Abstract Background Observational studies have found that both short and long sleep duration are associated with increased risk of metabolic syndrome (MetS). This study aimed to examine the associations of genetically determined sleep durations with MetS and its five components (i.e., central obesity, high blood pressure, dyslipidemia, hypertriglyceridemia, and hyperglycemia) among a group of elderly population. Methods In 335,727 participants of White British from the UK Biobank, linear Mendelian randomization (MR) methods were first employed to examine the causal association of genetically predicted continuous sleep duration with MetS and its each component. Nonlinear MR analyses were performed to determine the nonlinearity of these associations. The causal associations of short and long sleep duration with MetS and its components were further assessed by using genetic variants that associated with short (≤ 6 h) and long sleep (≥ 9 h) durations. Results Linear MR analyses demonstrated that genetically predicted 1-h longer sleep duration was associated with a 13% lower risk of MetS, a 30% lower risk of central obesity, and a 26% lower risk of hyperglycemia. Non-linear MR analyses provided evidence for non-linear associations of genetically predicted sleep duration with MetS and its five components (all P values

A quorum sensing based visualization reporter system is presented for the characterization of promoters in Gram-positive bacteria, utilizing violacein production, especially for use in the identification of secondary metabolites.

Abstract Rhynchaenus maculosus is an emerging insect pest with an increasingly serious tendency. Lack of biology information results in the bottleneck of integrated management of this pest. To facilitate an available design of integrated pest management strategy, biology of R. maculosus, including voltinism, life cycle, distribution, and damage has been investigated. Results reveal that R. maculosus is oligophagous and distributes in Heilongjiang, Jilin, and Liaoning provinces, China. This pest produces one generation per year (univoltinism) and overwinters as adults in leaf litter. From mid-April to late-April, active overwintering adults emerge from overwintering sites. The next generation of adult R. maculosus appears from mid-May to early June until mid-August to early September when the beetles move into the overwintering places. The entire time span of adult occurrence ranges from 315.6 ± 3.6 to 336.4 ± 3.2 days (Mean ± SD). Larvae undergo 3 instars with a total duration of 20 to 23 days. R. maculosus larvae feed on Q. wutaishanica and Q. mongolica without host-specific preference between the two host species, but do not harm Q. acutissim. Three species of larval parasites were collected and identified as Braconidae sp., Eulophidae sp., and Ceraphronidae sp. Biological information of R. maculosus provides essential insights for design and implementation of integrated management of this pest.

Background: Lactate, as an essential clinical evaluation index of septic shock, is crucial in the incidence and progression of septic shock. This study aims to investigate the differential expression, regulatory relationship, clinical diagnostic efficacy, and immune infiltration of lactate metabolism-related genes (LMGs) in septic shock.Methods: Two sepsis shock datasets (GSE26440 and GSE131761) were screened from the GEO database, and the common differentially expressed genes (DEGs) of the two datasets were screened out. LMGs were selected from the GeneCards database, and lactate metabolism-related DEGs (LMDEGs) were determined by integrating DEGs and LMGs. Protein-protein interaction networks, mRNA-miRNA, mRNA-RBP, and mRNA-TF interaction networks were constructed using STRING, miRDB, ENCORI, and CHIPBase databases, respectively. Receiver operating characteristic (ROC) curves were constructed for each of the LMDEGs to evaluate the diagnostic efficacy of the expression changes in relation to septic shock. Finally, immune infiltration analysis was performed using ssGSEA and CIBERSORT.Results: This study identified 10 LMDEGs, including LDHB, STAT3, LDHA, GSR, FOXM1, PDP1, GCDH, GCKR, ABCC1, and CDKN3. Enrichment analysis revealed that DEGs were significantly enriched in pathways such as pyruvate metabolism, hypoxia pathway, and immune-inflammatory pathways. PPI networks based on LMDEGs, as well as 148 pairs of mRNA-miRNA interactions, 243 pairs of mRNA-RBP interactions, and 119 pairs of mRNA-TF interactions were established. ROC curves of eight LMDEGs (LDHA, GSR, STAT3, CDKN3, FOXM1, GCKR, PDP1, and LDHB) with consistent expression patterns in two datasets had an area under the curve (AUC) ranging from 0.662 to 0.889. The results of ssGSEA and CIBERSORT both showed significant differences in the infiltration of various immune cells, including CD8 T cells, T regulatory cells, and natural killer cells, and LMDEGs such as STAT3, LDHB, LDHA, PDP1, GSR, FOXM1, and CDKN3 were significantly associated with various immune cells.Conclusion: The LMDEGs are significantly associated with the immune-inflammatory response in septic shock and have a certain diagnostic accuracy for septic shock.

The current study examined the possible predictors of dropout during a five-week light treatment (LT) with a gradual advance protocol in 93 patients with unipolar non-seasonal depression and evening chronotypes by comparing their clinical characteristics and performing a logistic regression analysis. Nineteen out of ninety-three (20%) subjects (80% female, 46.5 ± 11.7 years old) dropped out during the 5-week light treatment. Treatment non-adherence (i.e., receiving LT for less than 80% of the prescribed duration) over the first treatment week predicted a five-fold increase in risk of dropout during light therapy (OR: 5.85, CI: 1.41–24.21) after controlling for potential confounders, including age, gender, treatment group, rise time at the baseline, patient expectation, and treatment-emergent adverse events. There is a need to incorporate strategies to enhance treatment adherence and retention in both research and clinical settings. Chinese clinical trial registry (ChiCTR-IOR-15006937).

Abstract Patients with Parkinson’s disease (PD) were described less extraverted and more neurotic. It remained unclear whether similar personality traits could be found in idiopathic rapid eye movement sleep behavior disorder (iRBD), a prodromal stage of PD, and could predict phenoconversion to neurodegenerative disorders. We aimed to investigate the personality profile and its association with future neurodegenerative phenoconversion in iRBD patients. One hundred and eighty-five video-polysomnography confirmed iRBD patients and 91 age- and sex-matched controls underwent personality assessment using the NEO five-factor inventory, and 171 iRBD patients were followed up. Our results showed that iRBD was marginally negatively associated with extraverted personality trait (B = −0.28, 95% confidence interval (CI) = −0.55, −0.001). During a median follow-up of 5.9 years, 47 iRBD patients (27.5%) had phenoconversion. More neurotic (adjusted hazard ratio (HR) = 2.0, 95% CI = 1.3, 3.1) and less extraverted personality traits (adjusted HR = 0.53, 95% CI = 0.36, 0.77) were associated with an increased risk of phenoconversion in iRBD patients. Our findings suggest that personality profile may be a potential prodromal marker of iRBD.

Abstract Background Adverse ventricular structure and function is a key pathogenic mechanism of heart failure. Observational studies have shown that both insulin resistance (IR) and glycemic level are associated with adverse ventricular structure and function. However, whether IR and glycemic level are causally associated with cardiac structure and function remains unclear. Methods Genetic variants for IR, fasting insulin, HbA1c, and fasting glucose were selected based on published genome-wide association studies, which included 188,577, 108,557, 123,665, and 133,010 individuals of European ancestry, respectively. Outcome datasets for left ventricular (LV) parameters were obtained from UK Biobank Cardiovascular Magnetic Resonance sub-study (n = 16,923). Mendelian randomization (MR) analyses with the inverse-variance weighted (IVW) method were used for the primary analyses, while weighted median, MR-Egger, and MR-PRESSO were used for sensitivity analyses. Multivariable MR analyses were also conducted to examine the independent effects of glycemic traits on LV parameters. Results In the primary IVW MR analyses, per 1-standard deviation (SD) higher IR was significantly associated with lower LV end-diastolic volume (β = − 0.31 ml, 95% confidence interval [CI] − 0.48 to − 0.14 ml; P = 4.20 × 10−4), lower LV end-systolic volume (β = − 0.34 ml, 95% CI − 0.51 to − 0.16 ml; P = 1.43 × 10−4), and higher LV mass to end-diastolic volume ratio (β = 0.50 g/ml, 95% CI 0.32 to 0.67 g/ml; P = 6.24 × 10−8) after Bonferroni adjustment. However, no associations of HbA1c and fasting glucose were observed with any LV parameters. Results from sensitivity analyses were consistent with the main findings, but with a slightly attenuated estimate. Multivariable MR analyses provided further evidence for an independent effect of IR on the adverse changes in LV parameters after controlling for HbA1c. Conclusions Our study suggests that genetic liability to IR rather than those of glycemic levels are associated with adverse changes in LV structure and function, which may strengthen our understanding of IR as a risk factor for heart failure by providing evidence of direct impact on cardiac morphology.

C14H6N8O14Cl2, orthorhombic, Fdd2 (no. 43), a = 21.2891(12) Å, b = 39.532(3) Å, c = 5.1686(3) Å, V = 4349.9(4) Å3, Z = 8, R gt(F) = 0.0469, wR ref(F 2) = 0.1051, T = 140 K.

Abstract Background The fat‐to‐muscle mass ratio (FMR) might be an indicator to assess type 2 diabetes risk independent of general obesity. However, no longitudinal studies have explored the extent to which total and regional FMRs may confer risks. We aimed to measure the sex‐specific associations between FMRs of the arm, leg, trunk and whole body and incident type 2 diabetes. Methods A total of 464 817 participants (207 286 men and 257 531 women, mean age 56.5 ± 8.2 and 56.2 ± 8.0 years old, respectively) free of diabetes at baseline were included in this prospective cohort study with UK Biobank data. Fat mass and muscle mass were estimated using a bioelectrical impedance assessment device (Tanita BC 418MA). FMR was calculated as fat mass divided by muscle mass in corresponding body parts (total body, arm, leg and trunk). Cox proportional hazard models were used to estimate the aforementioned associations among men and women. Interaction analyses were performed between FMRs and body mass index (BMI) categories (BMI

Summary Salinomycin, an FDA‐approved polyketide drug, was recently identified as a promising anti‐tumour and anti‐viral lead compound. It is produced by Streptomyces albus, and the biosynthetic gene cluster (sal) spans over 100 kb. The genetic manipulation of large polyketide gene clusters is challenging, and approaches delivering reliable efficiency and accuracy are desired. Herein, a delicate strategy to enhance salinomycin production was devised and evaluated. We reconstructed a minimized sal gene cluster (mini‐cluster) on pSET152 including key genes responsible for tailoring modification, antibiotic resistance, positive regulation and precursor supply. These genes were overexpressed under the control of constitutive promoter PkasO* or Pneo. The pks operon was not included in the mini‐cluster, but it was upregulated by SalJ activation. After the plasmid pSET152::mini‐cluster was introduced into the wild‐type strain and a chassis host strain obtained by ribosome engineering, salinomycin production was increased to 2.3‐fold and 5.1‐fold compared with that of the wild‐type strain respectively. Intriguingly, mini‐cluster introduction resulted in much higher production than overexpression of the whole sal gene cluster. The findings demonstrated that reconstitution of sal mini‐cluster combined with ribosome engineering is an efficient novel approach and may be extended to other large polyketide biosynthesis.

Background We aimed to determine the associations of childhood maltreatment with incident heart failure in later life and explore the potentially modifying effects of genetic risk for heart failure on the associations. Methods and Results This cohort study included adults free of heart failure at baseline enrolled between 2006 and 2010 in the UK Biobank. Childhood maltreatment was retrospectively assessed with the online Childhood Trauma Screener in 2016. Five types of childhood maltreatment (range, 0–5), including physical abuse, physical neglect, emotional abuse, emotional neglect, and sexual abuse, were combined into a total score. A weighted polygenic risk score for heart failure was constructed. Incident all‐cause heart failure was prospectively ascertained via hospital inpatient and death records, followed up to May 31, 2021. A total of 153 287 adults (mean [SD] age, 55.9 [7.7] years; 43.6% male) were included. Over a median of 12.2 years (interquartile range, 11.5–12.9 years) of follow‐up, 2352 participants had incident heart failure. Childhood maltreatment was associated with a greater risk of incident heart failure in a dose‐response manner. One additional type of childhood maltreatment was associated with a 15% increase in the risk of developing heart failure (hazard ratio [HR], 1.15 [95% CI, 1.07–1.23]). There was no statistically significant interaction between genetic risk and childhood maltreatment (Pinteraction=0.218). Among participants with high genetic risk, those with 3 to 5 types of childhood maltreatment had a double hazard (HR, 2.00 [95% CI, 1.43–2.80]) of developing heart failure when taking those without any childhood maltreatment as the reference. Conclusions Irrespective of genetic risk for heart failure, childhood maltreatment was associated with an increased risk of incident heart failure in a dose‐dependent manner.

BackgroundElectronic media use (EMU) becomes one of the most common activities in adolescents. The present study investigated the deleterious influence of excessive EMU and EMU before bedtime on social, emotional, and behavioral difficulties (SEBD) in adolescents. The role of sleep and circadian problems in mediating the association of EMU with SEBD was examined.MethodsA cross-sectional survey study was conducted with 3,455 adolescents (55.7% female, mean age = 14.8 ± 1.57 years, 36.6% monthly family income < HK$15,000) between December 2011 and March 2012 in Hong Kong. The associations of EMU with sleep and circadian problems and SEBD were analyzed using multiple binary logistic regression and path analysis. Sleep problems were measured by the Insomnia Severity Index and the reduced Horne and Östberg Morningness and Eveningness Questionnaire. Circadian problems were calculated based on established formulas. SEBD was measured using the Strengths and Difficulties Questionnaire. Participants' mental health status was assessed by the General Health Questionnaire.ResultsA longer duration of EMU, excessive EMU (daily duration ≥ 2 h), and bedtime EMU (an hour before bedtime) were associated with the risk of sleep and circadian problems, poor mental health, and SEBD (p < 0.05). Insomnia, eveningness, social jetlag, and sleep deprivation were found to mediate the associations of EMU (including bedtime EMU of computers, electronic game consoles, phones, and televisions, together with excessive EMU of computers for leisure purposes and phones) with mental health and SEBD.ConclusionsThe findings suggest the need for setting up guidelines and advocacy for education for appropriate EMU and intervention for the associated sleep and circadian problems to ameliorate EMU-related mental and behavioral health problems in adolescents.

ObjectivesUnhealthy sleep behaviors may be potential risk factors for chronic kidney disease (CKD). We aimed to examine the associations of combined sleep patterns and genetic susceptibility with incident CKD.MethodsThis large-scale prospective cohort study included 370,671 participants without CKD at baseline (2006–2010) in UK Biobank data. Five sleep behaviors were made up of sleep duration, insomnia, snoring, chronotype, and daytime sleepiness according to questionnaire. Overall sleep patterns by summing the five scores were created. Weighted genetic risk score of kidney function was calculated. Incident CKD was recorded from death register, primary care, and hospital inpatient records. A subset of 41,130 individuals who participated both the initial assessment visit and follow-up visit (2012+) was also used.ResultsDuring a median follow-up of 10.6 years (about 3.9 million person-years), we documented 6,365 patients with incident CKD. In five sleep behaviors, sleep 7–8 h/day, free of insomnia and no frequent daytime sleepiness were independently associated with incident CKD, with a 12% (95%CI 7–16), 9% (3–14), 13% (9–18) lower risk, respectively. Compared to those with a sleep score of 0–1, participants with a score of 5 had a 21% (10–31%) lower risk of CKD. 17.1% of CKD in this cohort could be attributed to total poor sleep pattern. Participants with high genetic risk and intermediate or poor sleep pattern showed the highest risk of CKD (OR = 2.58, 95%CI 2.24–2.96; OR = 2.59, 95%CI 2.02–3.32, respectively), although there was no significant interaction between sleep patterns and genetic risk categories. Among individuals who participated both the initial assessment visit and follow-up visit, we found that the association between amelioration of sleep pattern and risk of CKD was significant after fully adjustment (OR = 0.60, 95%CI 0.36–0.99), compared with group of stable sleep pattern.ConclusionIn this large prospective study, participants with a healthy sleep pattern was associated with a significant reduction of incident CKD risk no matter they had a high, intermediate, or low genetic risk.

In this article we consider the multiplicity and concentration behavior of positive solutions for the fractional nonlinear Schrodinger equation $$\displaylines{ \varepsilon^{2s}(-\Delta)^{s}u + V(x)u= u^{2^*_s-1} + f(u) , \quad x\in\mathbb{R}^N,\cr u\in H^{s}(\mathbb{R}^N), \quad u(x) > 0, }$$ where $\varepsilon$ is a positive parameter, $s \in (0,1)$, N >2s and $2^*_s= \frac{2N}{N-2s}$ is the fractional critical exponent, and f is a $\mathcal{C}^{1}$ function satisfying suitable assumptions. We assume that the potential $V(x) \in \mathcal{C}(\mathbb{R}^N)$ satisfies $\inf_{\mathbb{R}^N} V(x)>0$, and that there exits k points $x^j \in \mathbb{R}^N$ such that for each j=1,...,k, $V(x^j)$ are strictly global minimum. By using the variational method, we show that there are at least $k$ positive solutions for a small $\varepsilon >0$. Moreover, we establish the concentration property of solutions as $\varepsilon$ tends to zero.

This paper develops an approach for solving the problem of least-cost transition firing sequences estimation in labeled Petri nets with unobservable transitions. Each transition in the net is labeled as either observable or unobservable, and has a nonnegative cost. Additionally, we assume that the net system is bounded, the unobservable subnet is acyclic, and the cost of each unobservable transition is strictly positive. We propose the method mainly on the basis of the notions of basis marking and basis reachability graph (BRG), which is a compact representation of the reachability graph of the net system. By sacrificing extra storage space to keep the BRG and other necessary information in memory, some time-consuming computations are moved off-line. This makes our proposed approach more feasible for on-line applications. Finally, we present a brief survey and comparison of some representative methods that use labeled Petri nets as a formalism in the literature.

Soil enzymes are involved in the process of mineralization of soil organic matters. The close-to-nature transformation (CNT) of plantations changes the soil enzyme activities by changing the composition of stand vegetation, which in turn affects the change process of soil organic carbon. We therefore selected two typical coniferous plantations in southwest China, Pinus massoniana and Cunninghamia lanceolate, to explore the effects of CNT on soil enzyme activities and soil organic carbon, and the relationship between them is explored through comparative study. Compared with control stands (CCK and PCK), CNT enhanced soil organic carbon; the content of water-soluble organic carbon in the 0–10 cm soil layer of the transformed C. lanceolata plantations (CCN) is 81.29% higher than those in the control stands (p < 0.05); the contents of particulate organic carbon and water-soluble organic carbon in the 10–30 cm soil layer are 95.42% and 48.68% higher than those in the control stands (p < 0.05), respectively; after the CNT, the protease, urease, and acid phosphatase in C. lanceolata plantations were higher than control stands, while protease and catalase in P. massoniana plantations were higher than control stands. Correlation analysis showed that catalase and protease were more closely related to organic carbon components than other organic enzymes; redundancy analysis (RDA) results show that pH and total nitrogen are key factors that cause changes in carbon fractions after the CNT. In general, CNT enhanced soil organic carbon in coniferous plantations, which was more conducive to soil organic carbon accumulation but had a negative effect on soil organic carbon stability to a certain extent. Therefore, the effect of tree species configuration on soil carbon stability components should be considered in the forest management practice.

Molecular junctions hold great potential for future microelectronics and attract people’s attention. Here, we used density functional theory calculations (DFT) to investigate the surface-enhanced Raman spectroscopy (SERS) and electron transport properties of fully π-conjugated oligomers (phenylacetylene)-3 (OPE-3) trapped in gold junctions. The effects of charge injection, an applied electric field, and molecular deformation are considered. We found that a new Raman peak located at around 1400 cm−1 appears after the injection of a charge, which agrees well with the experiment. The external electric field and configurational deformation hardly affect the Raman spectra, indicating that the electronic rather than the geometrical structure determines the Raman response. Nonequilibrium Green’s function (NEGF) calculations show that both the rotation of the benzene groups and an increased electrode distance largely reduced the conductivity of the studied molecular junctions. The present investigations provide valuable information on the effect of charging, electric field, and deformation on the SERS and conductivity of molecular junctions, helping the development of molecular devices.

Chlorothricin (CHL), produced by Streptomyces antibioticus DSM 40725 (wild-type strain, WT), belongs to a growing family of spirotetronate antibiotics that have biological activities inhibiting pyruvate carboxylase and malate dehydrogenase. ChlF2, a cluster-situated SARP regulator, can activate the transcription of chlJ, chlC3, chlC6, chlE1, chlM, and chlL to control CHL biosynthesis. Co-expression of chlF2 and chlK encoding type II thioesterase in WT strain under the control of Pkan led to high production of chlorothricin by 840% in comparison with that of WT. Since the inhibitory activity of CHL against several Gram-positive bacteria is higher than des-CHL, combinatorial strategies were applied to promote the conversion of des-CHL to CHL. Over-expression of chlB4, encoding a halogenase, combining with the supplementation of sodium chloride led to further 41% increase of CHL production compared to that of F2OE, a chlF2 over-expression strain. These findings provide new insights into the fine-tuned regulation of spirotetronate family of antibiotics and the construction of high-yield engineered strains.

BackgroundMobile phone addiction behaviors (MPAB) are extensively associated with several mental and sleep problems. Only a limited number of bidirectional longitudinal papers have focused on this field. This study aimed to examine the bidirectional associations of MPAB with mental distress, sleep disturbances, and sleep patterns.MethodsA total of 940 and 902 (response rate: 95.9%) students participated at baseline and one-year follow-up, respectively. Self-reported severity of mobile phone addiction was measured using Mobile Phone Involvement Questionnaire (MPIQ). Mental distress was evaluated by using Beck Depression Inventory (BDI) and Zung Self-Rating Anxiety Scale (SAS). Sleep disturbances were assessed by using Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS). Sleep patterns were evaluated by using reduced Morningness-Eveningness Questionnaire (rMEQ), weekday sleep duration, and weekend sleep duration.ResultsCross-lagged analyses revealed a higher total score of BDI, SAS, and ISI predicted a greater likelihood of subsequent MPAB, but not vice versa. We found the bidirectional longitudinal relationships between MPAB and the total score of PSQI and ESS. Besides, a higher score of MPIQ at baseline predicts a subsequent lower total score of rMEQ and shorter weekday sleep duration.ConclusionsThe current study expands our understanding of causal relationships of MPAB with mental distress, sleep disturbances, and sleep patterns.

ObjectiveThe outbreak of the 2019 novel coronavirus disease (COVID-19) not only caused particularly large public health problems, but also caused great psychological distress, especially for medical staff. We aimed to investigate the prevalence rate of insomnia and to confirm the related social psychological factors among medical staff in hospitals during the COVID-19 outbreak.MethodMedical staff members in China were recruited, including frontline medical workers. The questionnaire, administered through the WeChat program, obtained demographic data and asked self-design questions related to the COVID-19 outbreak, insomnia/depressive/anxiety symptoms, and stress-related symptoms. We used a logistic regression analysis to examine the associations between sociodemographic factors and insomnia symptoms.ResultThere were a total of 1,563 participants in our study. Five-hundred-and-sixty-four (36.1%) participants had insomnia symptoms according to the Insomnia Severity Index (ISI) (total score ≥ 8). A multiple binary logistic regression model revealed that insomnia symptoms were associated with an education level of high school or below (OR = 2.69, p = 0.042, 95% CI = 1.0–7.0), being a doctor (OR = 0.44, p = 0.007, 95% CI = 0.2–0.8), currently working in an isolation unit (OR = 1.71, p = 0.038, 95% CI = 1.0–2.8), is worried about being infected (OR = 2.30, p < 0.001, 95% CI = 1.6–3.4), perceived lack of helpfulness in terms of psychological support from news or social media with regard to COVID-19 (OR = 2.10, p = 0.001, 95% CI = 1.3–3.3), and having very strong uncertainty regarding effective disease control (OR = 3.30, p = 0.013, 95% CI = 1.3–8.5).ConclusionOur study found that more than one-third of the medical staff suffered insomnia symptoms during the COVID-19 outbreak. The related factors included education level, an isolation environment, psychological worries about the COVID-19 outbreak, and being a doctor. Interventions for insomnia among medical staff are needed considering the various sociopsychological factors at play in this situation.

With the increase of drug resistance caused by the improper use and abuse of antibiotics, human beings are facing a global health crisis. Sequencing of Streptomyces genomes revealed the presence of an important reservoir of secondary metabolic gene clusters for previously unsuspected products with potentially valuable bioactivity. It has therefore become necessary to activate these cryptic pathways through various strategies. Here, we used RNA-seq data to perform a comparative transcriptome analysis of Streptomyces ansochromogenes (wild-type, WT) and its global regulatory gene disruption mutant ΔwblA, in which some differentially expressed genes are associated with the abolished nikkomycin biosynthesis and activated tylosin analogue compounds (TACs) production, and also with the oviedomycin production that is induced by the genetic manipulation of two differentially expressed genes (san7324 and san7324L) encoding RsbR. These results provide a significant clue for the discovery of new drug candidates and the activation of cryptic biosynthetic gene clusters.

Objectives: We aimed to explore the potential mediating effects of neuroticism, depressive and anxiety symptoms, and somatic symptoms in the relationship between insomnia and health-related quality of life (HRQoL). Methods: This was a cross-sectional family study, which recruited a total of 297 adolescents (eighty insomniacs as determined by clinical interview) and 318 parents (93 insomniacs). HRQoL was measured by short form-36 (SF-36) health survey. A series of questionnaires were employed to measure insomnia severity, neuroticism personality, and depressive, anxiety and somatic symptoms. Results: Participants with insomnia had lower HRQoL than those without insomnia (71.9 vs. 77.1, P < 0.001). Insomnia severity (as measured byInsomnia Severity Index) was significantly associated with HRQoL (correlation coefficient = −0.451, P < 0.001). A total of 53% of the variance of SF-36 could be explained by the mediation model, which showed that a large proportion of the variances in the association between insomnia severity and HRQoL was mediated by depressive symptoms, somatic symptoms, and neuroticism personality trait. Conclusions: The close associations between insomnia severity and impaired HRQoL are largely mediated by psychological symptomatology and personality dimension. Further prospective study is warranted to investigate the long-term impact of insomnia symptoms on HRQoL and the roles of mood and somatic symptoms.

In this article we study a class of fractional Laplace equations which do not satisfy the Ambrosetti-Rabinowitz condition (AR-condition). We establish the existence of three nontrivial solutions and of multiple sign changing solutions by using Morse theory.

Habitat loss and degradation are among the leading causes of local extinctions, so it is crucially important to preserve and restore the remaining critical habitat increasingly critical to conserve biodiversity. However, mechanisms driving species extinction often begin with habitat loss and seldom are well understood, which is greatly limits our ability to mitigate their impacts. The Chinese Alligator (Alligator sinensis) is a critically endangered crocodilian, which is narrowly distributed in very small six regions of Anhui province, China. In the present study, we used 9 nuclear microsatellite loci genotyped across the taxon's distribution area to investigate genetic variation and population demography in A. sinensis. The Chinese Alligator showed unusually low levels of genetic diversity (Na, 5.44; Ne, 1.97; He, 0.47) based on 793 individuals. Msvar analyses found recent signals of population decline reflecting a bottleneck (an approximately 9-fold decrease) about 25,000 years ago. Ecological niche modelling indicated that the habitat area has declined (about 8–15 fold) for A. sinensis when compared with that under different historical climatic conditions. Our results indicated that population decline and habitat loss in critically endangered Chinese Alligators may have acted as intrinsic and extrinsic factors that have impacted the current status of A. sinensis. In addition, these two unfavorable factors may have also directly contributed to a reduction in the genetic diversity of A. sinensis. Keywords: Alligator sinensis, Genetic diversity, Population demography, Niche reconstruction

Objective: To investigate the impact of different slope directions on the quantity and quality of the soil seed bank and seedling germination process of Castanopsis hystrix plantations. Method: Fixed sample plots in forest stands of Castanopsis hystrix were established on different slope directions (sunny slope, semi-sunny slope, semi-shady slope, and shady slope). The characteristics of the forest stand were investigated, and per-wood scaling was carried out. The temporal dynamics of the seed rain and seed bank were quantified using seed rain collectors and by collecting soil samples from different depths. The quantity and quality of the seeds were determined, and the vigor of mature seeds was measured throughout the study. Results: (1) The diffusion of Castanopsis hystrix seed rain started in mid-September, reached its peak from late October to early November, and ended in mid-December. (2) The dissemination process, occurrence time, and composition of the seed rain varied between the different slope directions. The seed rain intensity on the semi-sunny slope was the highest (572.75 ± 9.50 grains∙m−2), followed by the sunny slope (515.60 ± 10.28 grains∙m−2), the semi-shady slope (382.13 ± 12.11 grains∙m−2), and finally the shady slope (208.00 ± 11.35 grains∙m−2). The seed rain on the sunny slope diffused earliest and lasted the longest, while the seed rain on the shady slope diffused latest and lasted the shortest time. Seed vigor and the proportion of mature seeds within the seed rain were greatest on the semi-sunny slope, followed by the sunny slope, semi-shady slope, and the shady slope. (3) From the end of the seed rain to August of the following year, the amount of total reserves of the soil seed banks was highest on the semi-sunny slope, followed by the sunny slope then the semi-shady slope, and it was the lowest on the shady slope. The amount of mature, immature, gnawed seeds and seed vigor of the soil seed bank in various slope directions showed a decreasing trend with time. The seeds of the seed bank in all slope directions were mainly distributed in the litter layer, followed by the 0–2 cm humus layer, and only a few seeds were present in the 2–5 cm soil layer. (4) The seedling density of Castanopsis hystrix differed significantly on the different slope directions. The semi-sunny slope had the most seedlings, followed by the sunny slope, semi-shady slope, and the shady slope. Conclusions: The environmental conditions of the semi-sunny slope were found to be most suitable for the seed germination and seedling growth of Castanopsis hystrix, and more conducive to the regeneration and restoration of its population.