Comparative molecular dynamics simulations provided insights into the mechanisms of cold-adaption of alginate lyases from the PL7 family.

Alginate is an important polysaccharide that is abundant in the marine environments, including the Polar Regions, and bacterial alginate lyases play key roles in its degradation. Many reported alginate lyases show characteristics of cold-adapted enzymes, including relatively low temperature optimum of activities (Topt) and low thermal stabilities. However, the cold-adaption mechanisms of alginate lyases remain unclear. Here, we studied the cold-adaptation mechanisms of alginate lyases by comparing four members of the PL7 family from different environments: AlyC3 from the Arctic ocean (Psychromonas sp. C-3), AlyA1 from the temperate ocean (Zobellia galactanivorans), PA1167 from the human pathogen (Pseudomonas aeruginosa PAO1), and AlyQ from the tropic ocean (Persicobacter sp. CCB-QB2). Sequence comparison and comparative molecular dynamics (MD) simulations revealed two main strategies of cold adaptation. First, the Arctic AlyC3 and temperate AlyA1 increased the flexibility of the loops close to the catalytic center by introducing insertions at these loops. Second, the Arctic AlyC3 increased the electrostatic attractions with the negatively charged substrate by introducing a high portion of positively charged lysine at three of the insertions mentioned above. Furthermore, our study also revealed that the root mean square fluctuation (RMSF) increased greatly when the temperature was increased to Topt or higher, suggesting the RMSF increase temperature as a potential indicator of the cold adaptation level of the PL7 family. This study provided new insights into the cold-adaptation mechanisms of bacterial alginate lyases and the marine carbon cycling at low temperatures.

Visual Cognitive Assessment Test: Utility of the brief cognitive battery for early screening of cognitive impairment in Chongqing, China.

OBJECTIVES: Early detection of cognitive impairment is essential for timely intervention. Currently, most widely used cognitive screening tests are influenced by language and cultural differences; therefore, there is a need for the development of a language-neutral, visual-based cognitive assessment tool. The Visual Cognitive Assessment Test (VCAT), a 30-point test that assesses memory, executive function, visuospatial function, attention, and language, has demonstrated its utility in a multilingual population. In this study, we evaluated the reliability, validity, and diagnostic performance of the VCAT for screening early cognitive impairment in Chongqing, China METHODS: A total of 134 individuals (49 healthy controls (HCs), 52 with mild cognitive impairment (MCI), and 33 with mild dementia) completed the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), VCAT, and domain-specific neuropsychological assessments. The diagnostic performances of MMSE, MoCA, and VCAT were evaluated using the area under the curve (AUC), sensitivity, and specificity. Construct validity of the VCAT was assessed with well-established domain-specific cognitive assessments. Reliability was measured using Cronbach's alpha. RESULTS: The VCAT and its subdomains demonstrated both good construct validity and internal consistency (α = 0.577). The performance of VCAT was comparable to that of MoCA and MMSE in differentiating mild dementia from nondemented groups (AUC: 0.940 vs. 0.902 and 0.977, respectively; p = .098 and .053) and in distinguishing cognitive impairment (CI) from HC (AUC: 0.929 vs. 0.899 and 0.891, respectively; p = .239 and .161), adjusted for education level. The optimal score range for VCAT in determining dementia, MCI, and HC was 0-14, 15-19, and 20-30, respectively. CONCLUSION: The VCAT proves to be a reliable screening test for early cognitive impairment within our cohort. Being both language and cultural neutral, the VCAT has the potential to be utilized among a wider population within China.

Annotation of 2,507 Saccharomyces cerevisiae genomes.

Saccharomyces cerevisiae (baker's yeast, budding yeast) is one of the most important model organisms for biological research and is a crucial microorganism in industry. Currently, a huge number of Saccharomyces cerevisiae genome sequences are available at the public domain. However, these genomes are distributed at different websites and a large number of them are released without annotation information. To provide one complete annotated genome data resource, we collected 2,507 Saccharomyces cerevisiae genome assemblies and re-annotated 2,506 assemblies using a custom annotation pipeline, producing a total of 15,407,164 protein-coding gene models. With a custom pipeline, all these gene sequences were clustered into families. A total of 1,506 single-copy genes were selected as marker genes, which were then used to evaluate the genome completeness and base qualities of all assemblies. Pangenomic analyses were performed based on a selected subset of 847 medium-high-quality genomes. Statistical comparisons revealed a number of gene families showing copy number variations among different organism sources. To the authors' knowledge, this study represents the largest genome annotation project of S. cerevisiae so far, providing rich genomic resources for the future studies of the model organism S. cerevisiae and its relatives.IMPORTANCESaccharomyces cerevisiae (baker's yeast, budding yeast) is one of the most important model organisms for biological research and is a crucial microorganism in industry. Though a huge number of Saccharomyces cerevisiae genome sequences are available at the public domain, these genomes are distributed at different websites and most are released without annotation, hindering the efficient reuse of these genome resources. Here, we collected 2,507 genomes for Saccharomyces cerevisiae, performed genome annotation, and evaluated the genome qualities. All the obtained data have been deposited at public repositories and are freely accessible to the community. This study represents the largest genome annotation project of S. cerevisiae so far, providing one complete annotated genome data set for S. cerevisiae, an important workhorse for fundamental biology, biotechnology, and industry.

Carbon emission change based on land use in Gansu Province.

Carbon emissions from land use change have become one of the main sources of regional carbon emissions. In order to explore the changes, 87 districts and counties in Gansu Province are taken as research objects. Based on the remote sensing data and statistical data of land use, the carbon emission coefficient method was used to investigate the spatial characteristics of land use carbon emission of each district and county in Gansu Province in recent 20 years from the perspective of carbon ecological support coefficient and per capita carbon footprint. The main results are as follows: (1) the growth of land use carbon emissions in Gansu Province from 2000 to 2020 was significant, but the growth of carbon emissions after 2010 was fast, and the growth of carbon sinks was relatively slow. (2) The ecological support coefficient of carbon emissions at county level in Gansu Province showed a trend of high in the south and low in the north, high in the east and low in the west, and this trend became more and more obvious with the passage of time. (3) Based on carbon emission, county population, and carbon ecological support capacity, the per capita carbon footprint of each county in Gansu Province was analyzed. The results showed that the per capita carbon footprint in Gansu Province was increasing, indicating that the gap between carbon emission and carbon absorption in each county was widening. By the above result, the author divides the counties of Gansu Province into three regions, low-carbon maintenance area, green development area, and ecological optimization area, and puts forward development suggestions for different regions, respectively. Therefore, this paper can also provide a theoretical reference for the formulation of carbon neutral planning measures in inland northwest China.

Unraveling the atmospheric oxidation mechanism and kinetics of naphthalene: Insights from theoretical exploration.

Naphthalene, the most abundant polycyclic aromatic hydrocarbon in the atmosphere, significantly influences OH consumption and secondary organic aerosol (SOA) formation. Naphthoquinone (NQ) is a significant contributor to ring-retaining SOA from naphthalene degradation, impacting the redox properties and toxicity of ambient particles. However, inconsistencies persist regarding concentrations of its isomers, 1,2-NQ and 1,4-NQ. In present work, our theoretical investigation into naphthalene's reaction with OH and subsequent oxygenation unveils their role in SOA formation. The reaction kinetics of initial OH and subsequent O2 oxidation was extensively studied using high-level quantum chemical methods (DLPNO-CCSD(T)/aug-ccpVQZ//M052x-D3/6-311++G(d,p)) combined with RRKM/master equation simulations. The reactions mainly proceed through electrophilic addition and abstraction from the aromatic ring. The total rate coefficient of naphthalene + OH at 300 K and 1 atm from our calculation (7.2 × 10-12 cm3 molecule-1 s-1) agrees well with previous measurements (∼1 × 10-11 cm3 molecule-1 s-1). The computed branching ratios facilitate accurate product yield determination. The largest yield of 1-hydroxynaphthalen-1-yl radical (add1) producing the major precursor of RO2 is computed to be 93.8 % in the ambient environment. Our calculated total rate coefficient (5.2 × 10-16 cm3 molecule-1 s-1) for add1 + O2 closely matches that of limited experimental data (8.0 × 10-16 cm3 molecule-1 s-1). Peroxy radicals (RO2) generated from add1 + O2 include 4-cis/trans-(1-hydroxynaphthalen-1-yl)-peroxy radical (add1-4OOadd-cis/trans, 66.0 %/17.5 %), 2-cis/trans-(1-hydroxynaphthalen-1-yl)-peroxy radical (add1-2OOadd-cis/trans, 10.3 %/6.3 %). Regarding the debated predominance of 1,4-NQ (corresponding to the parent RO2, i.e., add1-4OOadd-cis/trans) and 1,2-NQ (corresponding to the parent RO2, i.e., add1-2OOadd-cis/trans) in the atmosphere, our findings substantiate the dominance of 1,4-NQ. This study also indicates potential weakening of 1,4-NQ's dominance due to competition from decomposition reactions of add1-4OOadd-cis/trans and add1-2OOadd-cis/trans. Precise reaction kinetics data are essential for characterizing SOA transformation derived from naphthalene and assessing their climatic impacts within modeling frameworks.

Characteristics of carbon budget based on energy carbon emissions and vegetation carbon absorption.

How to evaluate the change characteristics of energy carbon emissions (ECE) and vegetation carbon absorption (VCA) by scientific methods is particularly important for achieving carbon peak by 2030 and carbon neutrality by 2060. Based on provincial-level energy consumption data, nighttime light data, and population data, this study realized spatial simulation of energy carbon emissions and analyzed the change characteristics of energy carbon emissions (ECE) and vegetation carbon absorption (VCA) combined with the net primary productivity (NPP)of vegetation. Besides, the relationship between energy carbon emissions, vegetation carbon absorption, and economic development was also analyzed at an urban scale. The results showed that (1) the total ECE increased from 4.34 billion tons in 2000 to 14.43 billion tons in 2019, but the growth rate of ECE decreased from 15.9% during 2000-2010 to 3.1% during 2010-2019. The VCA capacity has been increasing year by year. In 2019, it could absorb 1.56 billion tons more carbon dioxide than in 2000 with an increase of 16.1%. (2) Through the identification of the increasing and decreasing regions of ECE and VCA, it was found that the continuous rise area of ECE accounts for 0.5% of the study area; the area of fluctuating rise accounted for 6.7% of the study area. The area of continuous decline of VCA accounted for 0.2% of the study area; the area of fluctuating decline accounted for 49.6% of the study area. (3) The eastern China accounted for 42% of ECE and 17% of VCA with 11.4% of land, while the western region accounted for 26% of ECE and 55% of VCA with 66.6% of land, which indicated that there were significant differences in the characteristics of carbon budget between the eastern China and the western region. (4) The carbon pressure index (CPI) of most cities was on the rise, but the carbon efficiency index (CEI) was also on the rise, and cities were developing towards the model of low energy consumption and high output value. In a word, the growth rate of ECE is slowing down, and the VCA capacity is increasing. In the process of promoting carbon neutrality, we should be aware of the different resource endowments of different regions, realize the actual role of each region in carbon neutrality and economic development, and allocate carbon neutrality tasks differently.

A comprehensive drought index based on spatial principal component analysis and its application in northern China.

In the background of the greenhouse effect, drought events occurred more frequently. How to monitor drought events scientifically and efficiently is very urgent at present. In this study, we employed the Vegetation Water Supply Index (VSWI), Temperature Vegetation Drought Index (TVDI), and Crop Water Stress Index (CWSI) as individual variables to construct a composite drought index (CDI) using spatial principal component analysis (SPCA). The validity of CDI was assessed using gross primary productivity (GPP), soil moisture (SM), Standardized Precipitation Evapotranspiration Index (SPEI), and Vegetation Condition Index (VCI). CDI was subsequently used for drought monitoring in northern China from 2011 to 2020. The results showed that (1) at a 99% confidence level, the Pearson correlation coefficients between CDI and GPP was 0.72, while the value between CDI and SM was 0.69, which indicated the relationship between SM, GPP, and CDI was significant. (2) We compared CDI with other variables such as Standardized Precipitation Evapotranspiration Index (SPEI) and Crop Drought Index (CDI) and found that the monitoring result of CDI was more sensitive, which indicated that the proposed CDI had a better effect in local drought monitoring. (3) The results of CDI showed that the drought status in the northern region during 2011-2020 lasted from March to October, and the high severe drought period generally occurs in March-May and September-October, with low severe drought in June-August.

Genetic effect of metformin use on risk of cancers: evidence from Mendelian randomization analysis.

BACKGROUND: Increasing number of studies reported the positive effect of metformin on the prevention and treatment of cancers. However, the genetic causal effect of metformin utilization on the risk of common cancers was not completely demonstrated. METHODS: Two-sample Mendelian Randomization (two-sample MR) analysis was conducted to uncover the genetically predicted causal association between metformin use and 26 kinds of cancers. Besides, two-step Mendelian Randomization (two-step MR) assessment was applied to clarify the mediators which mediated the causal effect of metformin on certain cancer. We utilized five robust analytical methods, in which the inverse variance weighting (IVW) method served as the major one. Sensitivity, pleiotropy, and heterogeneity were assessed. The genetic statistics of exposure, outcomes, and mediators were downloaded from publicly available datasets, including the Open Genome-Wide Association Study (GWAS), FinnGen consortium (FinnGen), and UK Biobank (UKB). RESULTS: Among 26 kinds of common cancers, HER-positive breast cancer was presented with a significant causal relationship with metformin use [Beta: - 4.0982; OR: 0.0166 (95% CI: 0.0008, 0.3376); P value: 0.0077], which indicated metformin could prevent people from HER-positive breast cancer. Other cancers only showed modest associations with metformin use. Potential mediators were included in two-step MR, among which total testosterone levels (mediating effect: 24.52%) displayed significant mediating roles. Leave-one-out, MR-Egger, and MR-PRESSO analyses produced consistent outcomes. CONCLUSION: Metformin use exhibited a genetically protective effect on HER-positive breast cancer, which was partially mediated by total testosterone levels.

Insights into the composition and assembly mechanism of microbial communities on intertidal microsand grains.

Introduction: Marine microorganisms are essential in marine ecosystems and have always been of interest. Currently, most marine microbial communities are studied at the bulk scale (millimeters to centimeters), and the composition, function and underlying assembly mechanism of microbial communities at the microscale (sub-100 micrometers) are unclear. Methods: The microbial communities on microsand grains (40-100 µm, n = 150) from marine sediment were investigated and compared with those on macrosand grains (400-1000 µm, n = 60) and bulk sediments (n = 5) using amplicon sequencing technology. Results: The results revealed a significant difference between microsand grains and macrosand grains. Microsand grains had lower numbers of operational taxonomic units (OTUs(97%)) and predicted functional genes than macrosand grains and bulk-scale samples. Microsand grains also showed greater intersample differences in the community composition and predicted functional genes than macrosand grains, suggesting a high level of heterogeneity of microbial communities at the microscale. Analyses based on ecological models indicated that stochastic processes dominated the assembly of microbial communities on sand grains. Consistently, cooccurrence network analyses showed that most microbial cooccurrence associations on sand grains were highly unstable. Metagenomic sequencing and further genome-scale metabolic modeling revealed that only a small number (1.3%) of microbe pairs showed high cooperative potential. Discussion: This study explored the microbial community of marine sediments at the sub-100 µm scale, broadening the knowledge of the structure and assembly mechanism of marine microbial communities.

Enrichment Pretreatment Expands the Microbial Diversity Cultivated from Marine Sediments.

The majority of the microbial diversity in nature has not been recovered through cultivation. Enrichment is a classical technique widely used in the selective cultivation of specific taxa. Whether enrichment is suitable for cultivation studies that aim to recover large numbers of species remains little explored. To address this issue, we evaluated the potential of enrichment pretreatment in the cultivation of bacteria from marine sediments. Upon obtaining and classifying a total of 943 pure cultures from chitin and cellulose enrichment pretreatment systems and a control system, our results showed that species obtained using enrichment pretreatment differed greatly from those without enrichment. Multiple enrichment media and different enrichment times increased the number of cultivated species in a sample. Amplicon sequencing showed that the increased relative abundance during pretreatment contributed greatly to bacterial cultivation. The testing of degradation abilities against chitin and cellulose and the whole-genome sequencing of representative strains suggested that microorganism-microorganism interactions play roles in the expanded diversity of cultivated bacteria. This study provides new insights into the abilities of enrichment in exploring cultivable diversity and mining microbial resources.

Quantum mechanics/molecular mechanics studies on the excited-state decay mechanisms of cytidine aza-analogues: 5-azacytidine and 2'-deoxy-5-azacytidine in aqueous solution.

The excited state properties and deactivation pathways of two DNA methylation inhibitors, i.e., 5-azacytidine (5ACyd) and 2'-deoxy-5-azacytidine (5AdCyd) in aqueous solution, are comprehensively explored with the QM(CASPT2//CASSCF)/MM protocol. We systematically map the feasible decay mechanisms based on the obtained excited-state decay paths involving all the identified minimum-energy structures, conical intersections, and crossing points driving the different internal conversion (IC) and intersystem crossing (ISC) routes in and between the 1ππ*, 1nπ*, 3ππ*, 3nπ*, and S0 states. Unlike the 1nπ* state below the 1ππ* state in 5ACyd, deoxyribose group substitution at the N1 position leads to the 1ππ* state becoming the S1 state in 5AdCyd. In 5ACyd and 5AdCyd, the initially populated 1ππ* state mainly deactivates to the S0 state through the direct 1ππ* → S0 IC or mediated by the 1nπ* state. The former nearly barrierless IC channel of 1ππ* → S0 occurs ultrafast via the nearby low-lying 1ππ*/S0 conical intersection. In the latter IC channel of 1ππ* → 1nπ* → S0, the initially photoexcited 1ππ* state first approaches the nearby S2/S1 conical section 1ππ*/1nπ* and then undergoes efficient IC to the 1nπ* state, followed by the further IC to the initial S0 state via the S1/S0 conical intersection 1nπ*/S0. The 1nπ*/S0 conical intersection is estimated to be located 6.0 and 4.9 kcal mol-1 above the 1nπ* state minimum in 5ACyd and 5AdCyd, respectively, at the QM(CASPT2)/MM level. In addition to the efficient singlet-mediated IC channels, the minor ISC routes would populate 1ππ* to T1(ππ*) through 1ππ* → T1 or 1ππ* → 1nπ* → T1. Relatively, the 1ππ* → 1nπ* → T1 route benefits from the spin-orbit coupling (SOC) of 1nπ*/3ππ* of 8.7 cm-1 in 5ACyd and 10.2 cm-1 in 5AdCyd, respectively. Subsequently, the T1 system will approach the nearby T1/S0 crossing point 3ππ*/S0 driving it back to the S0 state. Given the 3ππ*/S0 crossing point located above the T1 minimum and the small T1/S0 SOC, i.e., 8.4 kcal mol-1 and 2.1 cm-1 in 5ACyd and 6.8 kcal mol-1 and 1.9 cm-1 in 5AdCyd, respectively, the slow T1 → S0 would trap the system in the T1 state for a while. The present work could contribute to understanding the mechanistic photophysics and photochemistry of similar aza-nucleosides and their derivatives.

Improved Interfacial Ion Migration and Deposition through the Chain-Liquid Synergistic Effect by a Carboxylated Hydrogel Electrolyte for Stable Zinc Metal Anodes.

The large-scale applicability of Zn-metal anodes is severely impeded by the issues such as the dendrite growth, complicated hydrogen evolution, and uncontrollable passivation reaction. Herein, a negatively charged carboxylated double-network hydrogel electrolyte (Gelatin/Sodium alginate-acetate, denoted as Gel/SA-acetate) has been developed to stabilize the interfacial electrochemistry, which restructures a type of Zn2+ ion solvent sheath optimized via a chain-liquid synergistic effect. New hydrogen bonds are reconstructed with water molecules by the zincophilic functional groups, and directional migration of hydrated Zn2+ ions is therefore induced. Concomitantly, the robust chemical bonding of such hydrogel layers to the Zn slab exhibits a desirable anti-catalytic effect, thereby greatly diminishing the water activity and eliminating side reactions. Subsequently, a symmetric cell using the Gel/SA-acetate electrolyte demonstrates a reversible plating/stripping performance for 1580 h, and an asymmetric cell reaches a state-of-the-art runtime of 5600 h with a high average Coulombic efficiency of 99.9 %. The resultant zinc ion hybrid capacitors deliver exceptional properties including the capacity retention of 98.5 % over 15000 cycles, energy density of 236.8 Wh kg-1 , and high mechanical adaptability. This work is expected to pave a new avenue for the development of novel hydrogel electrolytes towards safe and stable Zn anodes.

Optimal allocation for land in an arid inland basin in northwest China: framework and application based on CLUE-S and MCR models.

Reasonable planning of the limited land resources can promote the coordinated development of social economic and ecological protection. It is very important to optimize the rational distribution of land resources in the arid inland river basin because of the scarce land. In this paper, the GIS technologies of spatial analysis, conversion of land use, and its effects at small regional extent (CLUE-S) and minimum cumulative resistance (MCR) model were used to optimize the land allocation. The ecological security pattern (ESP) was constructed through using MCR model, which included ecological source and resistance surface. The dynamics of land use and spatial optimizing allocation of Shiyang River Basin in 2025 and 2030 was simulated under three different optimization scenarios including farmland protection scenario (FPS), free development scenario (FDS), and ecological security pattern scenario (ESPS). It was found that under ESPS, farmland was reduced, but woodland, grassland, and water body were increased significantly. Under FPS, land for construction was controlled effectively, a large part of homestead was converted into farmland, and the potential of unused land was developed vigorously. Furthermore, the current FDS and macro policy guidance should be comprehensively considered. The ESPS was more suitable for the scientific development of Shiyang River Basin on a long view. The combination of CLUE-S and MCR can effectively improve the optimization methods under ecological process and ecological resistance of landscape elements.

Mechanistic photophysics of tellurium-substituted cytosine: Electronic structure calculations and nonadiabatic dynamics simulations.

Previously, the MS-CASPT2 method was performed to study the static and qualitative photophysics of tellurium-substituted cytosine (TeC). To get quantitative information, we used our recently developed QTMF-FSSH dynamics method to simulate the excited-state decay of TeC. The CASSCF method was adopted to reduce the calculation costs, which was confirmed to provide reliable structures and energies as those of MS-CASPT2. A detailed structural analysis showed that only 5% trajectories will hop to the lower triplet or singlet state via the twisted (S2 /S1 /T2 )T intersection, while 67% trajectories will choose the planar intersections of (S2 /S1 /T3 /T2 /T1 )P and (S2 /S1 /T2 /T1 )P but subsequently become twisted in other electronic states. By contrast, ~28% trajectories will maintain in a plane throughout dynamics. Electronic population revealed that the S2 population will ultrafast transfer to the lower triplet or singlet state. Later, the TeC system will populate in the spin-mixed electronic states composed of S1 , T1 and T2 . At the end of 300 fs, most trajectories (~74%) will decay to the ground state and only 17.4% will survive in the triplet states. Our dynamics simulation verified that tellurium substitution will enhance the intersystem crossings, but the very short triplet lifetime (ca. 125 fs) will make TeC a less effective photosensitizer.

Effects of asymptomatic cerebral artery stenosis of anterior circulation and establishment of collateral circulation on cognition.

OBJECTIVE: The purpose of this study is to investigate how cognition is affected by asymptomatic cerebral artery stenosis (CAS) of the anterior circulation and its related collateral circulation. METHODS: 102 patients with CAS of the anterior circulation and 52 controls were enrolled from January 1, 2019 to June 30, 2022. Patients with CAS of anterior circulation were further divided into different subgroups according to the degree of stenosis, cerebral perfusion, and collateral circulation. A series of neuropsychological scales were used to evaluate the participant's cognitive function, activities of daily living, and neuropsychiatric symptoms (such as memory, execution, psychomotor speed, etc.). The data were analyzed using T-test, F-test, chi-square test, rank sum test, and other statistical methods, moreover, the quantitative data were further examined for trends. The relationship between the degree of CAS, cerebral perfusion, collateral circulation, and the outcome of the cognitive test was investigated using Spearman correlation analysis. RESULTS: Compared to controls, there were severe impairments of global cognition, psychomotor speed/execution, memory, attention, activities of daily living, and more neuropsychiatric symptoms in patients with anterior circulation CAS (p < 0.05), and these impairments got worsened with the aggravation of CAS (p < 0.05). The global cognition, psychomotor speed / executive function, memory function, and daily living ability were impaired both in the cerebral perfusion-compensated group and decompensated group(p < 0.05), while there was no statistically significant difference between the two groups (p > 0.05). With the aggravation of CAS, the proportion of poor collateral formation increased, and this difference was statistically significant (P < 0.01). The degree of stenosis, cerebral perfusion, and collateral circulation establishment of anterior circulation CAS was correlated with global cognition, memory, psychomotor speed, execution, attention, activities of daily living, and neuropsychiatric symptoms (all p < 0.01). CONCLUSION: Cognitive impairment and the percentage of inadequate collateral circulation development rise as stenosis progresses in patients with anterior circulation CAS. The decline in global cognitive function was accompanied by impairments in psychomotor speed / executive function, memory function, attention, and daily living skills, as well as the aggravation of neuropsychiatric symptoms, especially in patients with impaired cerebral perfusion and poor collateral circulation formation.

Phosphorus-Mediated Local Charge Distribution of N-Configuration Adsorption Sites with Enhanced Zincophilicity and Hydrophilicity for High-Energy-Density Zn-Ion Hybrid Supercapacitors.

Tailor-made carbonaceous-based cathodes with zincophilicity and hydrophilicity are highly desirable for Zn-ion storage applications, but it remains a great challenge to achieve both advantages in the synthesis. In this work, a template electrospinning strategy is developed to synthesize nitrogen and phosphorous co-doped hollow porous carbon nanofibers (N, P-HPCNFs), which deliver a high capacity of 230.7 mAh g-1 at 0.2 A g-1 , superior rate capability of 131.0 mAh g-1 at 20 A g-1 , and a maximum energy density of 196.10 Wh kg-1 at the power density of 155.53 W kg-1 . Density functional theory calculations (DFT) reveal that the introduced P dopants regulate the distribution of local charge density of carbon materials and therefore facilitate the adsorption of Zn ions due to the increased electronegativity of pyridinic-N. Ab initio molecular dynamics (AIMD) simulations indicate that the doped P species induce a series of polar sites and create a hydrophilic microenvironment, which decreases the impedance between the electrode and the electrolyte and therefore accelerates the reaction kinetics. The marriage of ex situ/in situ experimental analyses and theoretical simulations uncovers the origin of the enhanced zincophilicity and hydrophilicity of N, P-HPCNFs for energy storage, which accounts for the faster ion migration and electrochemical processes.

Understanding the Excited-State Relaxation Mechanisms of Xanthophyll Lutein by Multi-configurational Electronic Structure Calculations.

The contradictory behaviors in light harvesting and non-photochemical quenching make xanthophyll lutein the most attractive functional molecule in photosynthesis. Despite several theoretical simulations on the spectral properties and excited-state dynamics, the atomic-level photophysical mechanisms need to be further studied and established, especially for an accurate description of geometric and electronic structures of conical intersections for the lowest several electronic states of lutein. In the present work, semiempirical OM2/MRCI and multi-configurational restricted active space self-consistent field methods were performed to optimize the minima and conical intersections in and between the 1Ag-, 2Ag-, 1Bu+, and 1Bu- states. Meanwhile, the relative energies were refined by MS-CASPT2(10,8)/6-31G*, which can reproduce correct electronic state properties as those in the spectroscopic experiments. Based on the above calculation results, we proposed a possible excited-state relaxation mechanism for lutein from its initially populated 1Bu+ state. Once excited to the optically bright 1Bu+ state, the system will propagate along the key reaction coordinate, i.e., the stretching vibration of the conjugated carbon chain. During this period of time, the 1Bu- state will participate in and forms a resonance state between the 1Bu- and 1Bu+ states. Later, the system will rapidly hop to the 2Ag- state via the 1Bu+/2Ag- conical intersection. Finally, the lutein molecule will survive in the 2Ag- state for a relatively long time before it internally converts to the ground state directly or via a twisted S1/S0 conical intersection. Notably, though the photophysical picture may be very different in solvents and proteins, the current theoretical study proposed a promising calculation protocol and also provided many valuable mechanistic insights for lutein and similar carotenoids.

The genetically predicted causal relationship of inflammatory bowel disease with bone mineral density and osteoporosis: evidence from two-sample Mendelian randomization.

Background: Many existing studies indicated that patients with inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), tend to have the risk of low total body bone mineral density (BMD), and are more likely to have osteoporosis (OS). To determine the causal relationship between IBD and bone metabolic disorders, we herein performed a two-sample Mendelian randomization analysis (TSMR) using publicly available summary statistics. Methods: Summary statistics of total body BMD, OS and IBD were downloaded from the Open Genome-Wide Association Study (GWAS), FinnGen consortium and International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). The European and East Asian populations have consisted in this Mendelian Randomization (MR) work. A range of quality control procedures were taken to select eligible instrument SNPs closely associated with total body BMD, OS and IBD. To make the conclusions more reliable, we applied five robust analytical methods, among which the inverse variance weighting (IVW) method acted as the major method. Besides, heterogeneity, pleiotropy and sensitivity were evaluated. Results: In the European population, the genetic association of UC on total body BMD (OR=0.97, 95%CI=0.96,0.99, P<0.001) and overall IBD on total body BMD (OR=0.98, 95%CI=0.97,1.00, P=0.013) were significant, while the effect of CD on total body BMD was not significant enough (OR=0.99, 95%CI=0.98,1.00, P=0.085). All of UC, CD and overall IBD can be the genetic risk factor of having OS with pathological fracture (UC: OR=1.13, 95%CI=1.02,1.26, P=0.024, CD: OR=1.14, 95%CI=1.05,1.25, P=0.003, overall IBD: OR=1.13, 95%CI=1.02,1.24, P=0.015). In East Asian groups, only CD had a causal relationship with OS (OR=1.04, 95% CI=1.01,1.07, P=0.019). Conclusion: Our study revealed genetically predicted associations between IBD on total body BMD and OS in European and East Asian populations. This work supplemented the results of previous retrospective studies and demonstrated the necessity of BMD monitoring in patients with IBD.

Long noncoding RNA00324 is involved in the inflammation of rheumatoid arthritis by targeting miR-10a-5p via the NF-κB pathway.

BACKGROUND: Altered expressions of genes in immune cells and synovial tissues are involved in the pathology of rheumatoid arthritis (RA). Long noncoding RNAs act as competing endogenous RNAs and can cause immune disorders. The goal of this study was to reveal the association between noncoding RNA linc00324 and RA, and a plausible action mechanism was proposed. METHODS: RT-qPCR was used to evaluate the expression of linc00324 in peripheral blood mononuclear cells isolated from 50 RA patients and 50 healthy controls, and the correlations between linc00324 level and the clinical indicators were analyzed. Flow cytometry was used to characterize CD4+ T cells. The effects of linc00324 on cytokine production and cell proliferation of CD4+ T cells were evaluated by ELISA assay and Western blot. The interaction between linc00324 and miR-10a-5p was investigated by RNA immunoprecipitation and dual-luciferase assays. RESULTS: The linc00324 expression was significantly enhanced in RA patients, and linc00324 expression was positively correlated with rheumatoid factor and CD4+ T cells. Overexpression of linc00324 promoted CD4+ T cells proliferation, and enhanced chemokine MIP-1α secretion and NF-κB phosphorylation level, whereas knockout of linc00324 blocked CD4+ T cell proliferation and NF-κB phosphorylation. Overexpression of miR-10a-5p led to the decrease of CD4+ T cells proliferation and NF-κB phosphorylation, and reversed the effects of linc00324 on cell proliferation and NF-κB activity. CONCLUSION: Linc00324 was upregulated in RA and may exaggerate inflammation by targeting miR-10a-5p through NF-κB signaling pathway.

Prediction of risk factors for scrub typhus from 2006 to 2019 based on random forest model in Guangzhou, China.

OBJECTIVES: Scrub typhus is an increasingly serious public health problem, which is becoming the most common vector-borne disease in Guangzhou. This study aimed to analyse the correlation between scrub typhus incidence and potential factors and rank the importance of influential factors. METHODS: We collected monthly scrub typhus cases, meteorological variables, rodent density (RD), Normalised Difference Vegetation Index (NDVI), and land use type in Guangzhou from 2006 to 2019. Correlation analysis and a random forest model were used to identify the risk factors for scrub typhus and predict the importance rank of influencing factors related to scrub typhus incidence. RESULTS: The epidemiological results of the scrub typhus cases in Guangzhou between 2006 and 2019 showed that the incidence rate was on the rise. The results of correlation analysis revealed that a positive relationship between scrub typhus incidence and meteorological factors of mean temperature (Tmean ), accumulative rainfall (RF), relative humidity (RH), sunshine hours (SH), and NDVI, RD, population density, and green land coverage area (all p < 0.001). Additionally, we tested the relationship between the incidence of scrub typhus and the lagging meteorological factors through cross-correlation function, and found that incidence was positively correlated with 1-month lag Tmean , 2-month lag RF, 2-month lag RH, and 6-month lag SH (all p < 0.001). Based on the random forest model, we found that the Tmean was the most important predictor among the influential factors, followed by NDVI. CONCLUSIONS: Meteorological factors, NDVI, RD, and land use type jointly affect the incidence of scrub typhus in Guangzhou. Our results provide a better understanding of the influential factors correlated with scrub typus, which can improve our capacity for biological monitoring and help public health authorities to formulate disease control strategies.