Prolonged ventricular repolarization associated with mild cognitive impairment and white matter hyperintensities: a cross-sectional study.

Prolonged ventricular repolarization has been associated with cardiovascular disease. We sought to investigate the association of prolonged ventricular repolarization with mild cognitive impairment (MCI) and the potential underlying neuropathological mechanisms in older adults. This cross-sectional study included 4328 dementia-free participants (age ≥ 65 years; 56.8% female) in the baseline examination of the Multidomain INterventions to delay dementia and Disability in rural China; of these, 989 undertook structural brain magnetic resonance imaging (MRI) scans. QT, QTc, JT, JTc, and QRS intervals were derived from 12-lead electrocardiograph. MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI) were defined following the Petersen's criteria. Volumes of gray matter (GM), white matter, cerebrospinal fluid, total white matter hyperintensities (WMH), periventricular WMH (PWMH), and deep WMH (DWMH) were automatically estimated. Data were analyzed using logistic and general linear regression models. Prolonged QT, QTc, JT, and JTc intervals were significantly associated with an increased likelihood of MCI and aMCI, but not naMCI (p < 0.05). In the MRI subsample, QT, QTc, JT, and JTc intervals were significantly associated with larger total WMH and PWMH volumes (p < 0.05), but not with DWMH volume. Statistical interactions were detected, such that prolonged QT and JT intervals were significantly associated with reduced GM volume only among participants with coronary heart disease or without APOE ε4 allele (p < 0.05). Prolonged ventricular repolarization is associated with MCI and cerebral microvascular lesions in a general population of older adults. This underlies the importance of cognitive assessments and brain MRI examination among older adults with prolonged QT interval.

Oxytocin ameliorates cognitive impairments by attenuating excitation/inhibition imbalance of neurotransmitters acting on parvalbumin interneurons in a mouse model of sepsis-associated encephalopathy.

Inflammation plays a crucial role in the initiation and progression of sepsis, and it also induces alterations in brain neurotransmission, thereby contributing to the development of sepsis-associated encephalopathy (SAE). Parvalbumin (PV) interneurons are pivotal contributors to cognitive processes in various central dysfunctions including SAE. Oxytocin, known for its ability to augment the firing rate of gamma-aminobutyric acid (GABA)ergic interneurons and directly stimulate inhibitory interneurons to enhance the tonic inhibition of pyramidal neurons, has prompted an investigation into its potential effects on cognitive dysfunction in SAE. In the current study, we administered intranasal oxytocin to the SAE mice induced by lipopolysaccharide (LPS). Behavioral assessments, including open field, Y-maze, and fear conditioning, were used to evaluate cognitive performance. Golgi staining revealed hippocampal synaptic deterioration, local field potential recordings showed weakened gamma oscillations, and immunofluorescence analysis demonstrated decreased PV expression in the cornu ammonis 1 (CA1) region of the hippocampus following LPS treatment, which was alleviated by oxytocin. Furthermore, immunofluorescence staining of PV co-localization with vesicular glutamate transporter 1 or vesicular GABA transporter indicated a balanced excitation/inhibition effect of neurotransmitters on PV interneurons after oxytocin administration in the SAE mice, leading to improved cognitive function. In conclusion, cognitive function improved after oxytocin treatment. The number of PV neurons in the hippocampal CA1 region and the balance of excitatory/inhibitory synaptic transmission on PV interneurons, as well as changes in local field potential gamma oscillations in the hippocampal CA1 region, may represent its specific mechanisms.

Strategic Lacunes Associated With Mild Cognitive Impairment in Rural Chinese Older Adults: A Population-Based Study.

BACKGROUND: Lacunes are associated with cognitive impairment. We sought to identify strategic lacune locations associated with mild cognitive impairment (MCI) and subtypes of MCI among older adults, and further to examine the role of white matter hyperintensities and perivascular spaces in the association. METHODS: This population-based cross-sectional study included 1230 dementia-free participants in the brain magnetic resonance imaging substudy (2018-2020) in MIND-China (Multimodal Interventions to Delay Dementia and Disability in Rural China). Lacunes were visually identified in frontal lobe, parieto-occipital lobe, temporal lobe, insula, basal ganglia, thalamus, cerebellum, and brainstem. MCI, amnestic MCI (aMCI), and nonamnestic MCI (naMCI) were defined following the Petersen's criteria. Data were analyzed using logistic regression models. RESULTS: Of the 1230 participants (age, ≥60 years; mean age, 69.40; SD, 4.30 years; 58.5% women), lacunes were detected in 357 people and MCI was defined in 286 individuals, including 243 with aMCI and 43 with naMCI. Lacunes in the supratentorial area, internal capsula, putamen/pallidum, and insula was significantly associated with increased odds ratio of MCI (multivariable-adjusted odds ratio ranged 1.40-3.21; P<0.05) and aMCI (multivariable-adjusted odds ratio ranged 1.46-3.36; P<0.05), whereas lacunes in the infratentorial area and brainstem were significantly associated with naMCI (multivariable-adjusted odds ratio ranged 2.68-3.46; P<0.01). Furthermore, the associations of lacunes in insula and internal capsula with MCI and aMCI, as well as the associations of lacunes in infratentorial area and brainstem with naMCI were present independent of white matter hyperintensities volume and perivascular spaces number. CONCLUSIONS: Lacunes in the internal capsula, putamen/pallidum, insula, and brainstem may represent the strategic lacunes that are independently associated with MCI, aMCI, or naMCI in Chinese older adults. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800017758.

Isolation and characterisation of 17 microsatellite DNA loci from RAD reduced-representation genomes for Asian warty newts, genus Paramesotriton (Caudata: Salamandridae).

Asian warty newts, genus Paramesotriton, are endemic to southern China and northern Vietnam. Despite the achievements in biodiversity, molecular systematics and biogeography of species in this genus, population genetic diversity studies are lacking due to the lack of economical and available genetic markers. In this study, we developed 17 highly polymorphic microsatellite loci from RAD simplified genomic data for the Asian warty newts, genus Paramesotriton and successfully completed cross-species amplification tests on 20 samples of four species of Paramesotriton. These microsatellite markers can be used as important tools to study population genetic structure, levels of gene flow, population differentiation, mating systems and landscape genetics within the genus Paramesotriton and, thus, to make scientific conservation decisions and actions for the conservation of these rare and endangered amphibians.

Four new hypogean species of the genus Triplophysa (Osteichthyes, Cypriniformes, Nemacheilidae) from Guizhou Province, Southwest China, based on molecular and morphological data.

Recently described cave species of the genus Triplophysa have been discovered in southwestern China, suggesting that the diversity of the genus is severely underestimated and that there may be many undescribed species. In this work, four new species of the genus Triplophysa are described from southwestern Guizhou Province, China, namely Triplophysacehengensis Luo, Mao, Zhao, Xiao & Zhou, sp. nov. and Triplophysarongduensis Mao, Zhao, Yu, Xiao & Zhou, sp. nov. from Rongdu Town, Ceheng County, Guizhou, Triplophysapanzhouensis Yu, Luo, Lan, Xiao & Zhou, sp. nov. from Hongguo Town, Panzhou City, Guizhou, and Triplophysaanlongensis Song, Luo, Lan, Zhao, Xiao & Zhou, sp. nov. from Xinglong Town, Anlong County, Guizhou. These four new species can be distinguished from all recognized congeners by a combination of morphological characteristics and significant genetic divergences. The discovery of these species increases the number of known cave species within the genus Triplophysa to 39, making the genus the second most diverse group of cave fishes in China after the golden-line fish genus Sinocyclocheilus. Based on the non-monophyletic relationships of the different watershed systems in the phylogenetic tree, this study also discusses the use of cave species of the genus Triplophysa to determine the possible historical connectivity of river systems.

Veronica persica ameliorates acetaminophen-induced murine hepatotoxicity via attenuating oxidative stress and inflammation.

Excess acetaminophen (APAP) commonly causes severe acute liver injury (ALI), characterized by oxidative stress, pro-inflammatory responses, and hepatocyte damage. Veronica persica (VP) is a traditional medicine with antioxidant and anti-inflammatory properties. There is a paucity of information on its medicinal value, especially its potential mechanisms for alleviating ALI. This study aimed to clarify the ameliorative effects and intracellular mechanisms of VP on APAP-induced ALI via attenuating oxidative stress and inflammation. Mice were given VP for 7 days before exposure to APAP (300 mg/kg). The HPLC and radical scavenging assay found that VP contains 12 phenolic acids and 6 flavonoids, as well as show robust antioxidant capacity. In the APAP-induced ALI model, pre-treatment with VP significantly reduces APAP-induced hepatotoxicity by observing improved hepatocyte pathological injury and further confirmed by serum biochemical indicator. Also, the reduction of TUNEL-positive regions and the regulation of Bcl-2-associated X protein indicated that VP attenuates hepatocytotoxicity. Moreover, VP pre-intervention inhibits the formation of liver pro-inflammatory cytokines, the expression of inflammatory response genes, and increases in myeloperoxidase (MPO) in APAP-exposed mice. The elevated reduced glutathione (GSH) levels and decreased oxidative stress markers indicate that VP reduces APAP-promoted oxidative stress. Further study revealed that VP inhibited the phosphorylation of NF-κB/STAT3 cascade, blocked ERK and JNK phosphorylation, and activated AMP-activated protein kinase (AMPK). To sum up, this study demonstrated that VP exists hepatoprotective abilities on APAP-induced ALI, primarily by suppressing the phosphorylation of NF-κB/STAT3 cascade and ERK-JNK and inducing AMPK activation to alleviate oxidative stress and inflammation.

IGF2/IGF2R/Sting signaling as a therapeutic target in DSS-induced ulcerative colitis.

Ulcerative colitis is an inflammatory bowel disease with increasing prevalence and incidence. Current treatments for ulcerative colitis are not generally applicative and are often accompanied by side effects. IGF2 is an endogenous protein that plays roles in anti-inflammation and stemness maintenance, but little is known about its mechanism and function in the progression of ulcerative colitis. In this study, mouse recombinant IGF2 was used in a mouse model of ulcerative colitis established by DSS. IGF2 expression was reduced in colon tissues but not plasma of DSS-induced colitis mice. IGF2R expression was also decreased in colitis colons, which was then elevated by recombinant IGF2. Recombinant IGF2 alleviated colon injury in colitis, which was evaluated by colon shortening, body weight loss and DAI score. IGF2 treatment also relieved the inflammatory response in colitis, which was assessed by the spleen weight index, MPO activity and proinflammatory cytokine expression and was also detected in LPS-stimulated RAW264.7 cells in vitro. Moreover, IGF2R was predicted and further verified to interact with the Sting protein, and the cGAS-Sting pathway as a key pathway for stemness regulation, was upregulated in colonic colons, which was blocked by IGF2 treatment. Additionally, IGF2 treatment can maintain colonic stemness and further repair colonic tight junction function in DSS-induced colitis. In conclusion, IGF2/IGF2R downregulated the cGAS-Sting pathway to sustain colonic stemness and barrier integrity to protect against ulcerative colitis induced by DSS.

Accelerometer-Measured Sedentary Behavior Patterns, Brain Structure, and Cognitive Function in Dementia-Free Older Adults: A Population-Based Study.

BACKGROUND: Sedentary behavior is associated with cognitive impairment, but the neuropathological mechanisms underlying their associations are poorly understood. OBJECTIVE: To investigate the associations of accelerometer-measured sedentary behavior patterns with brain structure and cognition, and further to explore the potential mechanisms. METHODS: This community-based study included 2,019 older adults (age≥60 years, 59% women) without dementia derived from participants in the baseline examination of MIND-China (2018-2020). We assessed sedentary parameters using an accelerometer and cognitive function using a neuropsychological test battery. Structural brain markers were assessed on the structural brain MRI scans in a subsample (n = 1,009). Data were analyzed using the general linear, isotemporal substitution, and mediation models. RESULTS: In the total sample (n = 2,019), adjusting for multiple covariates and moderate-to-vigorous-intensity physical activity, longer mean sedentary bout duration was linearly related with lower z-scores of global cognition, verbal fluency, and memory (ptrend < 0.05), whereas greater total sedentary time was linearly associated with lower z-scores of global cognition, verbal fluency, and memory only among individuals with long sedentary time (>10 h/day) (ptrend < 0.05); Breaking up sedentary time with same amount of light-intensity physical activity was significantly associated with higher verbal fluency and memory z-scores (p < 0.05). In the MRI subsample (n = 1,009), separately entering structural brain MRI markers into the mediation models substantially attenuated the associations of mean sedentary bout duration with global cognition, verbal fluency, and memory z-scores. CONCLUSION: Prolonged uninterrupted sedentary time is associated with poor global cognition, memory, and verbal fluency among rural older adults, and structural brain markers could partially mediate the association.

Resting heart rate, cognitive function, and inflammation in older adults: a population-based study.

BACKGROUND: Emerging evidence has linked elevated resting heart rate (RHR) with poor cognitive function in older adults, but the mechanisms underlying their association are poorly understood. METHODS: This population-based cross-sectional study included 4510 dementia-free participants (age ≥ 65 years; 56.9% females; 38.3% no formal education) in the baseline examination of the Multidomain Interventions to Delay Dementia and Disability in Rural China study. Of these, 1,386 had data on serum proinflammatory cytokines and adhesion molecules. RHR was measured using 12-lead electrocardiograph. We used the Mini-Mental State Examination (MMSE) and a neuropsychological test battery to assess cognitive function. Data were analyzed using the general linear and restricted cubic splines models. RESULTS: People with high RHR were more likely to have cardiometabolic diseases and worse cognitive function (p < 0.05). There was an inverted J-shaped association of RHR with MMSE and attention scores. Having RHR ≥ 80 bpm (vs. 60-69 bpm) was significantly associated with the multivariable-adjusted ß coefficients of - 0.58 [95% confidence interval (CI), - 1.00, - 0.16] for MMSE score and - 0.08 (- 0.15, - 0.01) for attention score. In the serum biomarker subsample, RHR was linearly associated with serum interleukin-6 (IL-6) (ß coefficient = 0.19; 95%CI 0.14, 0.24), IL-8 (0.08; 0.02, 0.13), IL-10 (0.09; 0.04, 0.15), tumor necrosis factor-α (0.06; 0.01, 0.11), monocyte chemotactic protein-1 (0.09; 0.04, 0.15), intercellular adhesion molecule-1 (0.16; 0.11, 0.22), and vascular cell adhesion molecule-1 (0.11; 0.06, 0.16). CONCLUSIONS: There is an inverted J-shaped association of RHR with attention and global cognition. Poor cognitive function and high RHR may be linked through systemic low-grade inflammation and endothelial injury.

Comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for low-risk gestational trophoblastic neoplasia (FIGO Score 0-4): study protocol for a prospective, multicentre, randomized trial.

BACKGROUND: Single-agent chemotherapy using methotrexate or actinomycin D is the first-line treatment for patients with low-risk gestational trophoblastic neoplasia. Various methotrexate-based and actinomycin D-based single-agent regimens can be used. However, there is insufficient evidence to determine the superior regimen. To guide doctors in selecting a single-agent chemotherapy regimen for patients with low-risk gestational trophoblastic neoplasia, we will compare two regimens. METHODS: We will conduct a multicentre, randomized, prospective clinical trial. Selected low-risk gestational trophoblastic neoplasia patients (FIGO score 0-4) will be randomized 1:1 to a biweekly single-dose actinomycin D group or a multiday methotrexate therapy group. The actinomycin D group will receive IV pulse actinomycin D (1.25 mg/m2) every 14 days, and the methotrexate group will receive methotrexate (50 mg) intramuscularly on days 1, 3, 5, and 7 (4 doses per cycle) and leucovorin (15 mg) intramuscularly on days 2, 4, 6, and 8. This process will be repeated every 14 days. The primary endpoints will include the complete remission rate by single-agent therapy and the overall complete remission rate. The secondary endpoints will include the duration needed to achieve complete remission after single-agent chemotherapy, number of courses needed to achieve complete remission after single-agent chemotherapy, incidence and severity of adverse effects, effects on menstrual conditions and ovarian function based on the anti-Mullerian hormone level, and patient-reported quality of life. DISCUSSION: Previous clinical trials comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for treating low-risk gestational trophoblastic neoplasia patients failed to meet the expected case number. Through this multicentre study, the complete remission ratio and efficacy difference between biweekly single-dose actinomycin D and multiday methotrexate therapy will be obtained. This study will also provide the basis for formulating a preferred regimen for treating patients with low-risk gestational trophoblastic neoplasia. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04562558, Registered on 13 September 2020 (Protocol version 2020-9-24, version 1.0).

Ventricular Electrocardiographic Signatures Associated with Dementia and Plasma Alzheimer's Disease Biomarkers in Older Adults: A Population-Based Study.

BACKGROUND: Evidence has emerged that altered ventricular electrocardiogram profiles are associated with dementia, but the neuropathological mechanisms underlying their associations are poorly understood. OBJECTIVE: To investigate the interrelationships of ventricular electrocardiogram profiles with dementia and plasma Alzheimer's disease (AD) biomarkers among older adults. METHODS: This population-based cross-sectional study included 5,153 participants (age ≥65 years; 57.3% women) living in rural communities in China; of these, 1,281 had data on plasma amyloid-ß (Aß)40, Aß42, total-tau, and neurofilament light chain (NfL) protein. The QT, QTc, JT, JTc, QRS intervals, and QRS axis were derived from the 10-second electrocardiogram recording. The DSM-IV criteria were followed for clinical diagnosis of dementia, the NIA-AA criteria for AD, and the NINDS-AIREN criteria for vascular dementia (VaD). Data were analyzed using general linear models, multinomial logistic models, and restricted cubic splines. RESULTS: Of the 5,153 participants, 299 (5.8%) were diagnosed with dementia, including 194 with AD and 94 with VaD. Prolonged QT, QTc, JT, and JTc intervals were significantly associated with all-cause dementia, AD, and VaD (p < 0.05). Left QRS axis deviation was significantly associated with all-cause dementia and VaD (p < 0.01). In the subsample of plasma biomarkers (n = 1,281), prolonged QT, JT, and JTc intervals were significantly associated with a lower Aß42/Aß40 ratio and higher plasma NfL concentrations (p < 0.05). CONCLUSION: Alterations in ventricular repolarization and depolarization are independently associated with all-cause dementia, AD, VaD, and AD plasma biomarkers in older adults (age ≥65 years). Ventricular electrocardiogram parameters may be valuable clinical markers for dementia and the underlying AD pathologies and neurodegeneration.

Objectively-measured movement behaviors, systemic low-grade inflammation, and plasma neurofilament light chain in older adults: a population-based study.

BACKGROUND: Evidence has linked self-reported sedentary behavior (SB) and physical activity (PA) with cognitive impairment; however, the underlying mechanisms are poorly understood. We examined the associations of the accelerometer-measured movement behaviors with plasma neurofilament light chain (NfL) among older adults and the role of systemic low-grade inflammation in the associations. RESULTS: This population-based study included 1,029 dementia-free older adults (age ≥ 60 years, range 60-88 years; 59.48% women) who undertook the ActiGraph substudy (March 2018-December 2020) in MIND-China. There were nonlinear relationships of daily SB and PA time with plasma NfL concentration, such that more daily SB time or less time spent in daily light-intensity physical activity (LPA) and moderate-to-vigorous-intensity physical activity (MVPA) was significantly associated with increased plasma NfL only when SB time ≥ 8.00 h/day or LPA time < 5.00 h/day or MVPA time < 2.00 h/day. Furthermore, more daily SB time or less daily LPA and MVPA time was significantly associated with higher serum low-grade inflammation score, a composite measure generated from serum IL-6, IL-8, TNF-α, and ICAM-1 (P < 0.05). Finally, low-grade inflammation score accounted for 14.5% to 17.8% of the associations between movement behaviors and plasma NfL. CONCLUSIONS: More daily SB and less PA time are associated with neurodegeneration and systemic low-grade inflammation in older adults. The association of movement behaviors with neurodegeneration is partially mediated by low-grade inflammation.

Three-dimensional inter-layer optical signal transmission realized by a monolithically integrated semiconductor-based carrier transport structure.

In this study, we proposed and demonstrated a brand new type of monolithic photonic devices which realizes the three-dimensional (3D) all-optical switching for inter-layer signal transmission. This device is composed of a vertical Si microrod which serves as optical absorption material within a SiN waveguide in one layer and as an index modulation structure within a SiN microdisk resonator lying in the other layer. The ambipolar photo-carrier transport property in the Si microrod was studied by measuring the resonant wavelength shifts under continuous-wave laser pumping. The ambipolar diffusion length can be extracted to be 0.88 µm. Based on the ambipolar photo-carrier transport in a Si microrod through different layers, we presented a fully-integrated all-optical switching operation using this Si microrod and a SiN microdisk with a pump-probe technique through the on-chip SiN waveguides. The switching time windows for the on-resonance operation mode and the off-resonance operation mode can be extracted to be 439 ps and 87 ps, respectively. This device shows potential applications for the future all-optical computing and communication with more practical and flexible configurations in monolithic 3D photonic integrated circuits (3D-PICs).

Triglyceride-glucose index, Alzheimer's disease plasma biomarkers, and dementia in older adults: The MIND-China study.

Introduction: Population-based studies have rarely explored the associations of the triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, with dementia and plasma biomarkers for amyloid beta (Aß) and neurodegeneration. Methods: This population-based study included 5199 participants (age ≥ 65 years); of these, plasma Aß, total tau, and neurofilament light chain (NfL) were measured in 1287 persons. Dementia and subtypes were diagnosed following the international criteria. TyG index was calculated as ln(fasting triglyceride(mg/dL) × fasting glucose[mg/dL]/2). Data were analyzed using logistic and general linear regression models. Results: Dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were diagnosed in 301, 195, and 95 individuals, respectively. A high TyG index was significantly associated with increased likelihoods of dementia and AD; the significant association with dementia remained among participants without cardiovascular disease or diabetes. In the biomarker subsample, a high TyG index was correlated with elevated plasma Aß, but not with total tau or NfL. Discussion: High TyG index is associated with dementia, possibly via Aß pathology.

Trehalose promotes functional recovery of keratinocytes under oxidative stress and wound healing via ATG5/ATG7.

Wounds are in a stressed state, which precludes healing. Trehalose is a stress metabolite that protects cells under stress. Here, we explored whether trehalose reduces stress-induced wound tissue damage. A stress model was prepared by exposing human keratinocytes to hydrogen peroxide (H2O2), followed by trehalose treatment. Trehalose effects on expression of the autophagy-related proteins ATG5 and ATG7 and cell proliferation and migration were evaluated. For in vivo verification, a wound model was established in Sprague-Dawley rats, to measure the effects of trehalose wound-healing rate and reactive oxygen species (ROS) content. Histological changes during wound healing and trehalose's effects on ATG5 and ATG7 expression, necrosis, and apoptosis were examined·H2O2 stress increased ATG5 and ATG7 expression in vitro, but this was insufficient to prevent stress-induced damage. Trehalose further increased ATG5/ATG7 levels, which restored proliferation and increased migration by depolymerizing the cytoskeleton. However, trehalose did not exert these effects after ATG5 and ATG7 knockout. In vivo, the ROS content was higher in the wound tissue than in normal skin. Trehalose increased ATG5/ATG7 expression in wound tissue keratinocytes, reduced necrosis, depolymerized the cytoskeleton, and promoted cell migration, thereby promoting wound healing.

Associations of Cardiac Ventricular Repolarization with Serum Adhesion Molecules and Cognitive Function in Older Adults: The MIND-China Study.

BACKGROUND: Emerging evidence has linked electrocardiographic parameters with serum adhesion molecules and cognition; however, their interrelationship has not been explored. OBJECTIVE: We sought to investigate the associations of ventricular depolarization and repolarization intervals with serum adhesion molecules and cognitive function among rural-dwelling older adults. METHODS: This population-based study engaged 4,886 dementia-free participants (age ≥60 years, 56.2% women) in the baseline examination (March-September 2018) of MIND-China. Of these, serum intercellular and vascular adhesion molecules (ICAM-1 and VCAM-1) were measured in 1591 persons. We used a neuropsychological test battery to assess cognitive function. Resting heart rate, QT, JT intervals, and QRS duration were assessed with electrocardiogram. Data were analyzed using general linear models adjusting for multiple confounders. RESULTS: Longer JT interval was significantly associated with lower z-scores of global cognition (multivariable-adjusted ß= -0.035; 95% confidence interval = -0.055, -0.015), verbal fluency (-0.035; -0.063, -0.007), attention (-0.037; -0.065, -0.010), and executive function (-0.044; -0.072, -0.015), but not with memory function (-0.023; -0.054, 0.009). There were similar association patterns of QT interval with cognitive functions. In the serum biomarker subsample, longer JT and QT intervals remained significantly associated with poorer executive function and higher serum adhesion molecules. We detected statistical interactions of JT interval with adhesion molecules (pinteraction <0.05), such that longer JT interval was significantly associated with a lower executive function z-score only among individuals with higher serum ICAM-1 and VCAM-1. CONCLUSION: Longer ventricular depolarization and repolarization intervals are associated with worse cognitive function in older adults and vascular endothelial dysfunction may play a part in the associations.

Association of Accelerometer-Measured Sedentary Behavior Patterns With Nonalcoholic Fatty Liver Disease Among Older Adults: The MIND-China Study.

INTRODUCTION: The relationships between sedentary behavior patterns and nonalcoholic fatty liver disease (NAFLD) in older adults are not well investigated. METHODS: This population-based study included 1,899 rural-dwelling adults (aged 60 years or older). We assessed sedentary parameters with ActiGraph and defined NAFLD using ultrasonography. RESULTS: Long total and prolonged sedentary time were associated with increased likelihoods of NAFLD, whereas engaging more breaks per sedentary hour and reallocating sedentary time to light-intensity physical activity were associated with reduced likelihoods of NAFLD (P linear <0.05). DISCUSSION: Shorter sedentary time, engaging more frequent breaks in sedentary behavior, and replacing sedentary time with physical activity are associated with reduced likelihoods of NAFLD in older adults.

Comparison of Interobserver Agreement of Four Classification Systems for Lateral Clavicle Fractures between Two Groups of Surgeons: A Multicenter Study.

OBJECTIVE: Distal clavicle fracture classification directly affects the treatment decisions. It is unclear whether the classification systems implemented differ depending on surgeons' backgrounds. This study aimed to compare the interobserver agreement of four classification systems used for lateral clavicle fractures by shoulder specialists and general trauma surgeons. METHODS: Radiographs of 20 lateral clavicle fractures representing a full spectrum of adult fracture patterns were analyzed by eight experienced shoulder specialists and eight general trauma surgeons from 10 different hospitals. All cases were graded according to the Orthopedic Trauma Association (OTA), Neer, Jäger/Breitner, and Gongji classification systems. To measure observer agreement, Fleiss' kappa coefficient (κ) was applied and assessed. RESULTS: When only X-ray films were presented, both groups achieved fair agreement. However, when the 3D-CT scan images were provided, improved interobserver agreement was found in the specialist group when the OTA, Jäger/Breitner, and Gongji classification systems were used. In the generalist groups, improved agreement was found when using the Gongji classification system. In terms of interobserver reliability, the OTA, Neer, and Jäger/Breitner classification systems showed better agreement among shoulder specialists, while a slightly lower level of agreement was found using the Gongji classification system. For the OTA classification system, interobserver agreement had a mean kappa value of 0.418, ranging from 0.446 (specialist group) to 0.402 (generalist group). For the Neer classification system, interobserver agreement had a mean kappa value of 0.368, ranging from 0.402 (specialist group) to 0.390 (generalist group). For the Jäger/Breitner classification system, the inter-observer agreement had a mean kappa value of 0.380, ranging from 0.413 (specialist group) to 0.404 (generalist group). For the Gongji classification system, interobserver agreement had a mean kappa value of 0.455, ranging from 0.480 (specialist group) to 0.485 (generalist group). CONCLUSION: Generally speaking, 3D-CT scans provide a richer experience that can lead to better results in most classification systems of lateral clavicle fractures, highlighting the value of digitization and specialization in diagnosis and treatment. Competitive interobserver agreement was exhibited in the generalist group using the Gongji classification system, suggesting that the Gongji classification is suitable for general trauma surgeons who are not highly experienced in the shoulder field.

Disordered Expression of Tight Junction Proteins Is Involved in the Mo-induced Intestinal Microenvironment Dysbiosis in Sheep.

To evaluate the molybdenum (Mo)-induced changes of intestinal morphology and the relationship of intestinal tight junction (TJ) proteins expression and intestinal barrier function, a total of 20 healthy sheep were randomly divided into five groups of four: 0, 5, 10, 20, and 50 mg/kg BW/day Na2MoO4·2H2O were administrated in five groups named control group, Mo 5 group, Mo 10 group, Mo 20 group, and Mo 50 group, respectively. After 28 days of Mo treatment, the duodenum, the jejunum, and the ileum tissue were collected. The histopathology and the developmental parameters were evaluated by hematoxylin-eosin staining. The intestinal epithelial cell DNA damage was detected by TdT-mediated dUTP nick end labeling assay. The intestinal glycoprotein and the goblet cells were analyzed by Alcian Blue-Periodic Acid-Schiff (AB-PAS) staining and PAS staining, respectively. TJ proteins were determined by immunofluorescence technology. Results showed that excessive Mo significantly decreased the small intestinal villus height (VH), crypt depth (CD), VH/CD, and mucosal thickness (P < 0.05 or P < 0.01) while induced the damage of DNA in small intestinal epithelial cells. Moreover, excessive Mo injured intestinal barrier function by decreasing the percent of glycoprotein distribution area (P < 0.05) and the relative density of intestinal goblet cells (P < 0.05). Mo treatment induced decreased (P < 0.01) expression of Zonula Occludens-1, Occludin, and Claudin-1. In conclusion, excessive Mo interfered with the expression of TJ proteins, inhibited intestinal epithelial development, and further aggravated the intestinal barrier function damage, leading to disturbing the small intestinal microenvironment balance.

Interaction mechanism between nitrogen conversion and the microbial community in the hydrodynamic heterogeneous interaction zone.

To study the inorganic nitrogen in the process of interaction of river and groundwater and the changes in the microbial community, a vertical simulation device was used to simulate groundwater recharge to river water (upwelling) and river water recharge to groundwater (downwelling). The inorganic nitrogen concentrations in the soil and water solution as well as the characteristics of the microbial community were assessed to determine the inorganic nitrogen transformation and microbial community response in the heterogeneous interaction zone under hydrodynamic action, and the interaction mechanism between nitrogen transformation and the microbial community in the interaction zone was revealed. The removal rates of NO3--N in the simulated solution reached 99.1% and 99.3% under the two fluid-groundwater conversion modes, and the prolonged hydraulic retention time (HRT) of the oxidization-reduction layer in the fine clay area and the high organic matter content made the inorganic nitrogen transformation process dominated by microorganisms more complete. The denitrification during upwelling, dominated by denitrifying bacteria in Sphingomonas, Pseudomonas, Bacillus, and Arthrobacter, was stronger than that during downwelling. Dissimilatory nitrate reduction to ammonium (DNRA), controlled by some aerobic bacteria in Pseudomonas, Bacillus, and Desulfovibrio, was more intense in downflow mode than upflow mode.