Gut inflammation triggers C/EBPß/δ-secretase-dependent gut-to-brain propagation of Aß and Tau fibrils in Alzheimer's disease.

Inflammation plays an important role in the pathogenesis of Alzheimer's disease (AD). Some evidence suggests that misfolded protein aggregates found in AD brains may have originated from the gut, but the mechanism underlying this phenomenon is not fully understood. C/EBPß/δ-secretase signaling in the colon was investigated in a 3xTg AD mouse model in an age-dependent manner. We applied chronic administration of 1% dextran sodium sulfate (DSS) to trigger gut leakage or colonic injection of Aß or Tau fibrils or AD patient brain lysates in 3xTg mice and combined it with excision/cutting of the gut-brain connecting vagus nerve (vagotomy), in order to explore the role of the gut-brain axis in the development of AD-like pathologies and to monitor C/EBPß/δ-secretase signaling under those conditions. We found that C/EBPß/δ-secretase signaling is temporally activated in the gut of AD patients and 3xTg mice, initiating formation of Aß and Tau fibrils that spread to the brain. DSS treatment promotes gut leakage and facilitates AD-like pathologies in both the gut and the brain of 3xTg mice in a C/EBPß/δ-secretase-dependent manner. Vagotomy selectively blunts this signaling, attenuates Aß and Tau pathologies, and restores learning and memory. Aß or Tau fibrils or AD patient brain lysates injected into the colon propagate from the gut into the brain via the vagus nerve, triggering AD pathology and cognitive dysfunction. The results indicate that inflammation activates C/EBPß/δ-secretase and initiates AD-associated pathologies in the gut, which are subsequently transmitted to the brain via the vagus nerve.

A Stable Layered Microporous MOF Assembled with Y-O Chains for Separation of MTO Products.

Benefiting from highly tunable pore environments, some metal-organic frameworks (MOFs) have recently shown promising prospects in the separation of methanol-to-olefin (MTO) products (mainly C3H6 and C2H4). However, the "trade-off" between gas storage capacity and selectivity always results in inefficient separation. In addition, poor stability of MOFs also limits practical separation applications. Herein, we have successfully assembled a layered Y-MOF (FJI-W9) with bent diisophthalate ligands (H4L), Y-O chains, and 2-fluorobenzoic acids. As expected, FJI-W9 not only exhibits good chemical stability but also shows significant potential for C3H6/C2H4 separation. For FJI-W9, the C3H6 uptake at 298 K and 10 kPa is 63 cm3/g, and the IAST selectivity of FJI-W9 for C3H6/C2H4 (V/V = 50/50) is calculated to be 20.5. To the best of our knowledge, both C3H6 uptake and selectivity of FJI-W9 surpass most porous materials. GCMC simulation indicates that the special supramolecular binding sites in FJI-W9 have much stronger interactions with C3H6 than C2H4 molecules. More importantly, practical breakthrough experiments demonstrate that FJI-W9 can effectively separate C3H6/C2H4 (50/50) mixtures, thus obtaining high-purity C2H4 and C3H6, respectively.

Flexible Microporous Framework for One-Step Acquisition of Ethylene from Ternary C2 Hydrocarbons.

One-step purification of ethylene (C2H4) from ternary C2 hydrocarbon mixtures is a crucial task and an enduring challenge because of their similar molecular size and physical properties. Owing to their intriguing structural dynamics, flexible MOFs have attracted more attention for gas adsorption and separation. Herein, we report a flexible MOF FJI-W-66 that exhibits rarely seen "breathing" behaviors for C2 hydrocarbons. Upon activation, the channels of guest-free FJI-W-66a significantly contract to a nearly closed-pore state. FJI-W-66a shows the stepwise adsorption isotherms for C2 hydrocarbons, which suggests the occurrence of structural transformation between less open and more open phases. Breakthrough experiments provide evidence that FJI-W-66a can selectively separate C2H4 from C2H2/C2H4/C2H6 mixtures with different ratios under ambient conditions, realizing the one-step acquisition of C2H4 from ternary C2 hydrocarbons.

Global, regional, and national time trends in incidence for depressive disorders, from 1990 to 2019: an age-period-cohort analysis for the GBD 2019.

BACKGROUND: Even with advances in primary health care, depressive disorders remain a major global public health problem. We conducted an in-depth analysis of global, regional and national trends in depressive disorders incidence over the past 30 years. METHODS: Data on the incidence of depressive disorders were obtained by sex (female, male, and both), location (204 countries), age (5-84 years), year (1990-2019) from the Global Burden of Disease Study (GBD) 2019. Further, age-period-cohort modeling was used to estimate the net drift, local drift, age, period and cohort effects between 1990 and 2019. RESULTS: In 2019, although the incidence of depressive disorders has increased by 59.3% to 290 million (95% UI: 256, 328), the age-standardized incidence rate has decreased by 2.35% to 3588.25 per 100,000 people (3152.71, 4060.42) compared to 1990. There was an emerging transition of incidences from the young and middle-aged population to the old population. From 1990 to 2019, the net drift of incidence rate ranged from -0.54% (-0.61%, -0.47%) in low-middle Socio-demographic Index (SDI) regions to 0.52% (0.25%, 0.79%) in high SDI regions. Globally, the incidence rate of depressive disorders increases with age, period effects showing a decreasing risk and cohort effects beginning to decline after the 1960s. CONCLUSIONS: Our current findings reflect substantial health disparities and potential priority-setting of depressive disorders incidence in the three dimensions of age, period and cohort across SDI regions, countries. The scope of healthcare to improve the progression of depressive disorders events can be expanded to include males, females of all ages.

Synergistic C2H2 Binding Sites in Hydrogen-Bonded Supramolecular Framework for One-Step C2H4 Purification from Ternary C2 Mixture.

Purification of C2H4 from the ternary C2 hydrocarbon mixture in one step is of critical significance but still extremely challenging according to its intermediate physical properties between C2H6 and C2H2. Hydrogen-bonded organic frameworks (HOFs) stabilized by supramolecular interactions are emerging as a new kind of adsorbents that facilitate green separation. However, it remains a problem to efficiently realize the one-step C2H4 purification from C2H6/C2H4/C2H2 mixture because of the low C2H2/C2H4 selectivity. We herein report a robust microporous HOF (termed as HOF-TDCPB) with dense O atoms and aromatic rings distributed on the pore surface which provide C2H6 and C2H2 preferred environment simultaneously. Dynamic breakthrough experiments indicate that HOF-TDCPB can not only obtain high-purity C2H4 from binary C2 mixture, but also firstly realize one-step C2H4 purification from ternary C2H6/C2H4/C2H2 mixture, with the C2H4 productivity of 3.2 L/kg (>99.999 %) for one breakthrough cycle. Furthermore, HOF-TDCPB displays outstanding stability in air, organic solvents and water, which endow it excellent cycle performance even under high-humidity conditions. Theoretical calculations indicate that multiple O sites on pore channels can create synergistic binding sites for C2H2, thus affording overall stronger multipoint interactions.

Ideal Cage-like Pores for Molecular Sieving of Butane Isomers with High Purity and Record Productivity.

n-C4H10 and iso-C4H10 are both important petrochemical raw materials. Considering the coexistence of the isomers in the production process, it is necessary to achieve their efficient separation through an economical way. However, to obtain high-purity n-C4H10 and iso-C4H10 in one-step separation process, developing iso-C4H10-exclusion adsorbents with high n-C4H10 adsorption capacity is crucial. Herein, we report a cage-like MOF (SIFSIX-Cu-TPA) with small windows and large cavities which can selectively allow smaller n-C4H10 enter the pore and accommodate a large amount of n-C4H10 simultaneously. Adsorption isotherms reveal that SIFSIX-Cu-TPA not only completely excludes iso-C4H10 in a wide temperature range, but also exhibits a very high n-C4H10 adsorption capacity of 94.2 cm3 g-1 at 100 kPa and 298 K, which is the highest value among iso-C4H10-exclusion-type adsorbents. Breakthrough experiments show that SIFSIX-Cu-TPA has excellent n/iso-C4H10 separation performance and can achieve a record-high productivity of iso-C4H10 (3.2 mol kg-1) with high purity (>99.95 %) as well as 3.0 mol kg-1 of n-C4H10 (>99 %) in one separation circle. More importantly, SIFSIX-Cu-TPA can realize the efficient separation of butanes at different flow rates, temperatures, as well as under high humid condition, which indicates that SIFSIX-Cu-TPA can be deemed as an ideal platform for industrial butane isomers separation.

Testing for the Markov property in time series via deep conditional generative learning.

The Markov property is widely imposed in analysis of time series data. Correspondingly, testing the Markov property, and relatedly, inferring the order of a Markov model, are of paramount importance. In this article, we propose a nonparametric test for the Markov property in high-dimensional time series via deep conditional generative learning. We also apply the test sequentially to determine the order of the Markov model. We show that the test controls the type-I error asymptotically, and has the power approaching one. Our proposal makes novel contributions in several ways. We utilise and extend state-of-the-art deep generative learning to estimate the conditional density functions, and establish a sharp upper bound on the approximation error of the estimators. We derive a doubly robust test statistic, which employs a nonparametric estimation but achieves a parametric convergence rate. We further adopt sample splitting and cross-fitting to minimise the conditions required to ensure the consistency of the test. We demonstrate the efficacy of the test through both simulations and the three data applications.

Global, regional, and national time trends in incidence for migraine, from 1990 to 2019: an age-period-cohort analysis for the GBD 2019.

BACKGROUND: The majority of epidemiological studies on migraine have been conducted in a specific country or region, and there is a lack of globally comparable data. We aim to report the latest information on global migraine incidence overview trends from 1990 to 2019. METHODS: In this study, the available data were obtained from the Global Burden of Disease 2019. We present temporal trends in migraine for the world and its 204 countries and territories over the past 30 years. Meanwhile, an age-period-cohort model be used to estimate net drifts (overall annual percentage change), local drifts (annual percentage change in each age group), longitudinal age curves (expected longitudinal age-specific rate), and period (cohort) relative risks. RESULTS: In 2019, the global incidence of migraine increased to 87.6 million (95% UI: 76.6, 98.7), with an increase of 40.1% compared to 1990. India, China, United States of America, and Indonesia had the highest number of incidences, accounting for 43.6% of incidences globally. Females experienced a higher incidence than males, the highest incidence rate was observed in the 10-14 age group. However, there was a gradual transition in the age distribution of incidence from teenagers to middle-aged populations. The net drift of incidence rate ranged from 3.45% (95% CI: 2.38, 4.54) in high-middle Socio-demographic Index (SDI) regions to -4.02% (95% CI: -4.79, -3.18) in low SDI regions, 9 of 204 countries showed increasing trends (net drifts and its 95% CI were > 0) in incidence rate. The age-period-cohort analysis results showed that the relative risk of incidence rate generally showed unfavorable trends over time and in successively birth cohorts among high-, high-middle-, and middle SDI regions, but low-middle- and low-SDI regions keep stable. CONCLUSIONS: Migraine is still an important contributor to the global burden of neurological disorders worldwide. Temporal trends in migraine incidence are not commensurate with socioeconomic development and vary widely across countries. Both sexes and all age groups should get healthcare to address the growing migraine population, especially adolescents and females.

Tuning Pore Polarization to Boost Ethane/Ethylene Separation Performance in Hydrogen-Bonded Organic Frameworks.

Hydrogen-bonded organic frameworks (HOFs) show great potential in energy-saving C2 H6 /C2 H4 separation, but there are few examples of one-step acquisition of C2 H4 from C2 H6 /C2 H4 because it is still difficult to achieve the reverse-order adsorption of C2 H6 and C2 H4 . In this work, we boost the C2 H6 /C2 H4 separation performance in two graphene-sheet-like HOFs by tuning pore polarization. Upon heating, an in situ solid phase transformation can be observed from HOF-NBDA(DMA) (DMA=dimethylamine cation) to HOF-NBDA, accompanied with transformation of the electronegative skeleton into neutral one. As a result, the pore surface of HOF-NBDA has become nonpolar, which is beneficial to selectively adsorbing C2 H6 . The difference in the capacities for C2 H6 and C2 H4 is 23.4 cm3 g-1 for HOF-NBDA, and the C2 H6 /C2 H4 uptake ratio is 136 %, which are much higher than those for HOF-NBDA(DMA) (5.0 cm3 g-1 and 108 % respectively). Practical breakthrough experiments demonstrate HOF-NBDA could produce polymer-grade C2 H4 from C2 H6 /C2 H4 (1/99, v/v) mixture with a high productivity of 29.2 L kg-1 at 298 K, which is about five times as high as HOF-NBDA(DMA) (5.4 L kg-1 ). In addition, in situ breakthrough experiments and theoretical calculations indicate the pore surface of HOF-NBDA is beneficial to preferentially capture C2 H6 and thus boosts selective separation of C2 H6 /C2 H4 .

A Noncovalent π-Stacked Porous Organic Molecular Framework for Selective Separation of Aromatics and Cyclic Aliphatics.

Selective separation using porous adsorbents is an energy-efficient alternative to traditional separation techniques. Stacked porous organic molecular frameworks (POMFs) capable of noncovalent π⋅⋅⋅π interactions are emerging as a new kind of adsorbents that facilitate green separation. Here we report a robust porous molecular crystal (TAPM-1), which is stabilized by multiple intermolecular π⋅⋅⋅π interactions. With its long-range π-stacking, TAPM-1 has excellent hydrophobicity, thermostability, recyclability, and high selectivity for aromatics over the corresponding cyclic aliphatics. This enables TAPM-1 to serve as the stationary phase in the high-resolution gas chromatographic separation of benzene and cyclohexane or toluene and methylcyclohexane.

Testing Directed Acyclic Graph via Structural, Supervised and Generative Adversarial Learning.

In this article, we propose a new hypothesis testing method for directed acyclic graph (DAG). While there is a rich class of DAG estimation methods, there is a relative paucity of DAG inference solutions. Moreover, the existing methods often impose some specific model structures such as linear models or additive models, and assume independent data observations. Our proposed test instead allows the associations among the random variables to be nonlinear and the data to be time-dependent. We build the test based on some highly flexible neural networks learners. We establish the asymptotic guarantees of the test, while allowing either the number of subjects or the number of time points for each subject to diverge to infinity. We demonstrate the efficacy of the test through simulations and a brain connectivity network analysis.

Water-Stable Microporous Bipyrazole-Based Framework for Efficient Separation of MTO Products.

Recently, methanol-to-olefins (MTO) technology has been widely used. The development of new adsorbents to separate MTO products and obtain high-purity ethylene (C2H4) and propylene (C3H6) has become an urgent task. Herein, an exceptionally highly water-stable metal-organic framework (MOF), [Cu3(OH)2(Me2BPZ)2]·(solvent)x (1) (H2Me2BPZ = 3,3'-dimethyl-1H,1'H-4,4'-bipyrazole) with hexagonal pores, has been elaborately designed and constructed. After being soaked in water for 7 days, it still maintains its structure, and the uptake of N2 at 77 K is unchanged. The adsorption capacity of C3H6 can reach 138 cm3 g-1, while the uptake of C2H4 is only 52 cm3 g-1 at 298 K and 1 bar. The dynamic breakthrough experiments show that the mixture of C3H6/C2H4 (50/50, v/v) can be efficiently separated in one step. High-purity C2H4 and C3H6 can be obtained through an adsorption and desorption cycle and the yields of C2H4 (purity ≥ 99.95%) and C3H6 (purity ≥ 99%) are 84 and 48 L kg-1, respectively. Surprisingly, when the flow rate is increased, the separation performance has no obvious change. Additionally, humidity has no effect on the separation performance. Finally, theoretical simulations indicate that there are stronger interactions between the C3H6 molecule and the framework, which are beneficial to capturing C3H6 over C2H4.

Visualization and bibliometric analysis of occupational exposure among nurses in Asia.

Background: Occupational exposure is of increasing concern, posing a serious threat to nurses, especially in the event of a public health emergency. Bibliometrics sheds novel light on the current state of research and factors influencing nurses' occupational exposures, illuminating hot topics and trends in the literature. Bibliometrics is essential to analyze the potential harm to nurses in Asia. Methods: Data were extracted from the Web of Science Core Collection on August 6, 2022 with the following search terms: TS= (nurses) AND (TS= (occupational exposure OR occupational health)). CiteSpace and VOSviewer were used to analyze national and institutional collaborations, reference clustering, citations and co-citations of journals and keyword bursts, and HistCite was used to analyze the citation historiography map. To analyze the data and generate statistical charts, Origin and Microsoft Excel were utilized. Results: A total of 1448 studies on nurses' occupational exposure in Asia were identified. China Medical University had the most publications among Asian institutions, and China had the largest share among Asian countries. Most articles on nurses' occupational exposure in Asia were in the Journal of Occupational Health, and the journal with the highest impact factor was the Journal of Nursing Management. The COVID-19 outbreak caused a substantial shift in the direction of studies on nurses' occupational exposure in Asia. Mental health is a current hot topic, while sharps injuries and bodily fluid exposure are long-term priorities for attention. Conclusions: The hotspots of research on nurses' occupational exposure in Asia focus on mental health, burnout, blood exposure, infection, and sharps injury. Due to the COVID-19 pandemic, recent research has concentrated on personalized mental health care and the development of protective equipment, and cross-disciplinary collaboration may be a new trend in the future.

Gut Microbiota Changes and Their Correlation with Cognitive and Neuropsychiatric Symptoms in Alzheimer's Disease.

BACKGROUND: Gut microbiota can influence human brain function and behavior. Recent studies showed that gut microbiota might play an important role in the pathogenesis of Alzheimer's disease (AD). OBJECTIVE: To investigate the composition of gut microbiota in AD patients and their association with cognitive function and neuropsychiatric symptoms (NPS). METHODS: The fecal samples from 60 AD patients (30 with NPS and 30 without NPS) and 32 healthy control subjects (HC) were collected and analyzed by 16S ribosomal RNA sequencing. The functional variations of gut microbiota were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States. The correlation between different bacterial taxa and cognitive (Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR)), and NPS measures were analyzed. RESULTS: The fecal microbial composition of AD patients was quite distinct from HC. Bifidobacterium, Sphingomonas, Lactobacillus, and Blautia were enriched, while Odoribacter, Anaerobacterium, and Papillibacter were reduced. AD patients with NPS showed decreased Chitinophagaceae, Taibaiella, and Anaerobacterium compared with those without NPS. Functional pathways were different between AD and HC, and between AD patients with and without NPS. Correlation analysis showed that Sphingomonas correlated negatively with MMSE; Anaerobacterium and Papillibacter correlated positively with MMSE and negatively with CDR. Cytophagia, Rhodospirillaceae, and Cellvibrio correlated positively with NPS, while Chitinophagaceae, Taibaiella, and Anaerobacterium correlated negatively with NPS. CONCLUSION: AD patients have gut microbiota alterations related to cognition, and differential taxa between AD patients with and without NPS associated differently with NPS domains, which helps further understand the pathogenesis of AD and explore potential therapeutic targets.

CCR7 pathway induces epithelial-mesenchymal transition through up-regulation of Snail signaling in gastric cancer.

The chemokine receptor 7 (CCR7) and Snail signaling have been linked to various types of cancers. The associations between these signalings and the epithelial-mesenchymal transition (EMT) are not clear in gastric cancer. Here, the expression of CCR7 and Snail was detected in gastric cancer by immunohistochemistry and Western blot. Meanwhile, gastric cancer cells were subjected to CCL19, si-control, and si-Snail treatment. Cell cycle, migration, and invasion were also analyzed. The expression patterns of CCR7 and Snail were similar in either gastric cancer tissues or cells. The increased expression of CCR7 was closely associated with the increased Snail expression, which both were closely correlated with metastasis, stage and differentiation, and poor prognosis. The increased p-ERK, p-AKT, Snail, and MMP9 expression and the decreased E-cadherin were confirmed in MGC803 cells in a dose-dependent manner in response to CCL19 treatment. However, the blockade of Snail abrogated the up-regulation of MMP9 and down-regulation of E-cadherin. CCR7-induced ERK and PI3K pathway regulated Snail signaling. Besides si-Snail treatment led to MGC803 cell cycle arrest and affected the migration and invasion. In conclusion, our study suggested that CCR7 promotes Snail expression to induce the EMT, resulting in cell cycle progression, migration, and invasion in gastric cancer. CCR7-Snail pathway provided more potential regimens for cancer therapy.