Lewis Acidic Metal-Organic Framework Assisted Ambient Liquid Extraction Mass Spectrometry Imaging for Enhancing the Coverage of Poorly Ionizable Lipids in Brain Tissue.

The spatial distribution of lipidomes in tissues is of great importance in studies of living processes, diseases, and therapies. Mass spectrometry imaging (MSI) has become a critical technique for spatial lipidomics. However, MSI of low-abundance or poorly ionizable lipids is still challenging because of the ion suppression from high-abundance lipids. Here, a metal-organic framework (MOF) Zr6O4(OH)4(1,3,5-Tris(4-carboxyphenyl) benzene)2(triflate)6(Zr6OTf-BTB) was prepared and used for selective on-tissue adsorption of phospholipids to reduce ion suppression from them to poorly ionizable lipids. The results show that Zr6OTf-BTB with strong Lewis acidic sites and a large specific surface area (647.9 m2·g-1) could selectively adsorb phospholipids under 1% FA-MeOH. Adsorption efficiencies of phospholipids are 88.4-144.9 times higher than those of other neutral lipids. Moreover, the adsorption capacity and the adsorption kinetic rate constant of the new material to phospholipids are higher than those of Zr6-BTB (242.72 vs 73.96 mg·g-1, 0.0442 vs 0.0220 g·mg-1·min-1). A Zr6OTf-BTB sheet was prepared by a lamination technique for on-tissue phospholipid adsorption from brain tissue. Then, the tissue section on the Zr6OTf-BTB sheet was directly imaged via ambient liquid extraction-MSI with 1% FA-MeOH as the sampling solvent. The results showed that phospholipids could be 100% removed directly on tissue, and the detection coverage of the Zr6OTf-BTB-enhanced MSI method to ceramides (Cers) and hexosylceramides (HexCers) was increased by 5-26 times compared with direct tissue MSI (26 vs 1 and 17 vs 3). The new method provides an efficient and convenient way to eliminate the ion suppression from phospholipids in MSI, largely improving the detection coverage of low-abundance and poorly ionizable lipids.

Pulled Flowprobe for Ambient Liquid Extraction-Based High Spatial Resolution Mass Spectrometry Imaging with Enhanced Sensitivity and Stability.

Ambient liquid extraction techniques enable direct mass spectrometry imaging (MSI) under ambient conditions with minimal sample preparation. However, currently an integrated probe for ambient liquid extraction-based MSI with high spatial resolution, high sensitivity, and stability is still lacking. In this work, we developed a new integrated probe made of pulled coaxial capillaries, named pulled flowprobe, and compared it with the previously reported single-probe. Mass transfer kinetics in probes was first investigated. The extraction kinetic curves during probe sampling indicate a narrower and higher peak shape for the pulled flowprobe than single-probe. Computational fluid dynamics analysis reveals that in the pulled flowprobe flow velocities are lower in liquid microjunction and higher in the transferring channels, resulting in higher extraction efficiencies and reduced band diffusion compared with single-probe and other probes with a similar flow route. Results of ambient liquid extraction-based MSI of lipids in rat cerebrum show that signals of low-abundance lipids were 2-5 times higher via a pulled flowprobe than via a single-probe, and 26 more lipid species were detected on brain tissue via a pulled flowprobe than via a single-probe. The stability of MSI with the pulled flowprobe was found to be higher than that with single-probe (averaged relative standard deviation = 18% vs 80%) by imaging a lab-made uniform ink coating. Moreover, in the pulled flowprobe, no retraction of the inner capillary from outer capillary is optimal for both sensitivity and stability. The spatial resolution of the pulled flowprobe (30-40 µm) was measured to be higher than that of a comparable size single-probe by calculation with the "80-20" rule. Finally, the new pulled flowprobe was applied to high-resolution MSI of lipids in the hippocampus, and localization of several lipids to the specific cell layers in the hippocampus region was observed. Thus, this work provides an alternative easily fabricated sampling probe with enhanced sensitivity, stability, and spatial resolution, promoting the use of ambient liquid extraction-based MSI in biological and clinical research.

Light at night and cause-specific mortality risk in Mainland China: a nationwide observational study.

BACKGROUND: While epidemiological studies have found correlations between light at night (LAN) and health effects, none has so far investigated the impacts of LAN on population mortality yet. We aimed to estimate the relative risk for mortality from exposure to LAN in Mainland China. METHODS: This time-stratified case-crossover nationwide study used NPP-VIIRS to obtain daily LAN data of Mainland China between 2015 and 2019. The daily mortality data were obtained from the Disease Surveillance Point System in China. Conditional Poisson regression models were applied to examine the relative risk (RR) for mortality along daily LAN in each county, then meta-analysis was performed to combine the county-specific estimates at the national or regional level. RESULTS: A total of 579 counties with an average daily LAN of 4.39 (range: 1.02-35.46) were included in the main analysis. The overall RRs per 100 nW/cm2/sr increases in daily LAN were 1.08 (95%CI: 1.05-1.11) for all-cause mortality and 1.08 (95%CI: 1.05-1.11) for natural-cause mortality. A positive association between LAN and all natural cause-specific mortality was observed, of which the strongest effect was observed on mortality caused by neuron system disease (RR = 1.32, 95%CI: 1.14-1.52). The results were robust in both younger and old, as well as in males and females. The more pronounced effect of LAN was observed in median LAN-level regions. Combined with an exposure-response curve, our study suggests a non-linear association between LAN and mortality in China. CONCLUSIONS: Our study shows LAN is associated with mortality in China, particularly for neuron system disease-related mortality. These findings have important implications for public health policy establishment to minimize the health consequences of light pollution.

Mortality and years of life lost due to pancreatic cancer in China, its provinces, urban and rural areas from 2005 to 2020: results from the national mortality surveillance system.

BACKGROUND: Pancreatic cancer is a growing public health concern in China, and depicting it from different perspectives would provide a comprehensive understanding of its epidemiological characteristics. METHODS: Data from the National Mortality Surveillance System (NMSS) in China was used to estimate the number of deaths, years of life lost (YLL), age-standardized mortality rate (ASMR) and age-standardized YLL rate in China, its provinces and urban-rural areas from 2005 to 2020. Joinpoint regression analysis was employed to explore the temporal trends of ASMR and age-standardized YLL rate. Decomposition analysis was conducted to assess the contribution of population growth, population aging and cause-specific mortality rate to the increment of pancreatic cancer deaths. RESULTS: A total of 100,427 pancreatic cancer deaths and 2,166,355 pancreatic cancer related YLL were estimated in China in 2020. The overall ASMR significantly increased from 6.6/100 000 in 2005 to 7.4/100 000 in 2020, and was higher in men than that in women. Age-standardized YLL rate showed a similar trend. The mortality rates of pancreatic cancer were generally higher in northeast China than in southwest China. The highest ASMRs were found in Jilin, Zhejiang, Inner Mongolia and Anhui, and the lowest ones in Guangxi, Yunnan, Tibet, and Hainan. The disease burden due to pancreatic cancer presented a significant upward trend in rural areas and a downward trend in urban areas. CONCLUSIONS: The burden associated with pancreatic cancer had been increasing in China from 2005 to 2020. The escalating disease burden of pancreatic cancer in rural areas necessitates the implementation of effective control and prevention measures. Relevant provinces should pay greater attention to the prevailing of pancreatic cancer, particularly those exhibiting higher mortality rates.

Can global or national disability weights represent provincial level?

BACKGROUND: A universal set of disability weights(DWs) is mainly based on the survey of North America, Australia and Europe, whereas the participants in Asia was limited. The debate hasn't yet settled whether a universal DW is desirable or useful.The focus of the debate is its representativenes-s.After all, the DWs come from people's subjective evaluation of pain, and they may vary according to cultural background.The differences of the DWs could have implications for the magnitude or ranking of disease burdens.The DWs of Anhui Province has not been completely presented.This paper aims to obtain the DWs suitable for the general population of Anhui Province of China, and attempts to explore the differences between different DWs by comparing the DWs with the similar-cultural background and the DWs with cross-cultural background. METHODS: A web-based survey was conducted to estimate the DWs for 206 health states of Anhui province in 2020. Paired comparison (PC) data were analyzed and anchored by probit regression and fitting loess model. We compared the DWs in Anhui with other provinces in China and those in Global burden of disease (GBD) and Japan. RESULTS: Compared with Anhui province, the proportion of health states which showed 2 times or more differences ranged from 1.94% (Henan) to 11.17% (Sichuan) in China and domestic provinces. It was 19.88% in Japan and 21.51% in GBD 2013 respectively. In Asian countries or regions, most of the health states with top 15 DWs belonged to the category of mental, behavioral, and substance use disorders. But in GBD, most were infectious diseases and cancer. The differences of DWs in neighboring provinces were smaller than other geographically distant provinces or countries. CONCLUSION: PC responses were largely consistent across very distinct settings,but the exceptions do need to be faced squarely.The differences of DWs among similar-cultural regions were smaller than cross-cultural regions. There is an urgent need for relevant gold standards.

Association between ambient sulfur dioxide pollution and asthma mortality: Evidence from a nationwide analysis in China.

There is a lack of research on the effects of acute exposure to ambient sulfur dioxide (SO2) on mortality caused by asthma, especially nationwide research in China. To explore the acute effect of exposure to ambient SO2 on asthma mortality using nationwide dataset in China from 2015 to 2020 and further evaluate the associations in subgroups with different geographical and demographic characteristics. We used data from China's Disease Surveillance Points system with 29,553 asthma deaths in China during 2015-2020. The exposure variable was the daily mean concentrations of SO2 from the ChinaHighSO2 10 km × 10 km daily grid dataset. Bilinear interpolation was used to estimate each individual's exposure to air pollutants and meteorological variables. We used a time-stratified case crossover design at the individual level to analyze the exposure response relationship between short-term exposure to SO2 and asthma mortality. Stratified analyses were carried out by sex, age group, marital status, warm season and cold season, urbanicity and region. Significant associations between short-term exposure to ambient SO2 and increased asthma mortality were found in this nationwide study. The excess risk (ER) for each 10 µg/m3 increase in SO2 concentrations at lag07 was 7.78 % (95 % CI, 4.16-11.52 %). Season appeared to significantly modify the association. The associations were stronger in cold season (ER 9.78 %, 95 % CI:5.82 -13.89 %). The association remained consistent using different lag periods, adjusting for other pollutants, and in the analysis during pre-Corona Virus Disease 2019 (COVID-19) period. Our study indicates increased risk of asthma mortality with acute exposures to SO2 in Chinese population. The current study lends support for greater awareness of the harmful effect of SO2 in China and other countries with high SO2 pollution.

Structural Evolution and Electronic Properties of Selenium-Doped Boron Clusters SeBn0/- (n = 3-16).

A theoretical research of structural evolution, electronic properties, and photoelectron spectra of selenium-doped boron clusters SeBn0/- (n = 3-16) is performed using particle swarm optimization (CALYPSO) software in combination with density functional theory calculations. The lowest energy structures of SeBn0/- (n = 3-16) clusters tend to form quasi-planar or planar structures. Some selenium-doped boron clusters keep a skeleton of the corresponding pure boron clusters; however, the addition of a Se atom modified and improved some of the pure boron cluster structures. In particular, the Se atoms of SeB7-, SeB8-, SeB10-, and SeB12- are connected to the pure quasi-planar B7-, B8-, B10-, and B12- clusters, which leads to planar SeB7-, SeB8-, SeB10-, and SeB12-, respectively. Interestingly, the lowest energy structure of SeB9- is a three-dimensional mushroom-shaped structure, and the SeB9- cluster displays the largest HOMO-LUMO gap of 5.08 eV, which shows the superior chemical stability. Adaptive natural density partitioning (AdNDP) bonding analysis reveals that SeB8 is doubly aromatic, with 6 delocalized π electrons and 6 delocalized σ electrons, whereas SeB9- is doubly antiaromatic, with 4 delocalized π electrons and 12 delocalized σ electrons. Similarly, quasi-planar SeB12 is doubly aromatic, with 6 delocalized π electrons and 14 delocalized σ electrons. The electron localization function (ELF) analysis shows that SeBn0/- (n = 3-16) clusters have different local electron delocalization and whole electron delocalization effects. The simulated photoelectron spectra of SeBn- (n = 3-16) have different characteristic bands that can identify and confirm SeBn- (n = 3-16) combined with future experimental photoelectron spectra. Our research enriches the geometrical structures of small doped boron clusters and can offer insight for boron-based nanomaterials.

Trend of nasopharyngeal carcinoma mortality and years of life lost in China and its provinces from 2005 to 2020.

To examine the trends of nasopharyngeal carcinoma (NPC) mortality and years of life lost (YLL) in China and its provinces from 2005 to 2020, our study used data from China National Mortality Surveillance System (NMSS) to estimate the number and rate of mortality and YLL of NPC by age and sex. We calculated average annual percent change (AAPC) to describe the trend of NPC mortality and YLL over time. We also analyzed the proportion of NPC deaths in all cancer deaths and explored the drivers of change in NPC deaths by decomposition analysis. The age-standardized mortality rate (ASMR) of NPC in China had a significant downward trend from 2.0/100 000 in 2005 to 1.4/100 000 in 2020 (AAPC = -2.4, P < .05). Age-standardized YLL rate also showed the similar trends (AAPC = -2.8, P < .05). Southern provinces including Guangdong (163.9/100 000), Guangxi (130.5/100 000), and Hainan (105.6/100 000) had the highest YLL rate in 2020. The mortality and YLL rate increased with age and males were higher than females. From 2005 to 2020, the proportion of NPC deaths in all cancer deaths remained stable at around 1.0% in China. The total number of deaths of NPC increased by 7.3%, of which age-specific mortality, population growth, and population aging accounted for -46.2%, 8.5% and 45.0%, respectively. NPC remains a significant public health issue in China southern provinces and tailored prevention and control strategies should be strengthened to reduce the burden of premature mortality of NPC in high risk areas.

AgNAC1, a celery transcription factor, related to regulation on lignin biosynthesis and salt tolerance.

The NAC transcription factor participates in various biotic and abiotic stress responses and plays a critical role in plant development. Lignin is a water-insoluble dietary fiber, but it is second only to cellulose in abundance. Celery is the main source of dietary fiber, but its quality and production are limited by various abiotic stresses. Here, AgNAC1 containing the NAM domain was identified from celery. AgNAC1 was found to be a nuclear protein. Transgenic Arabidopsis thaliana plants hosting AgNAC1 have longer root lengths and stomatal axis lengths than the wide type (WT). The evidence from lignin determination and expression levels of lignin-related genes indicated that AgNAC1 plays a vital role in lignin biosynthesis. Furthermore, the results of the physiological characterization and the drought and salt treatments indicate that AgNAC1-overexpressing plants are significantly resistive to salt stress. Under drought and salt treatments, the AgNAC1 transgenic Arabidopsis thaliana plants presented increased superoxide dismutase (SOD) and peroxidase (POD) activities and decreased malondialdehyde (MDA) content and size of stomatal apertures relatively to the WT plants. The AgNAC1 served as a positive regulator in inducing the expression of stress-responsive genes. Overall, the overexpressing AgNAC1 enhanced the plants' resistance to salt stress and played a regulatory role in lignin accumulation.

Validation and cost-effectiveness of an in-house dithiothreitol (DTT) treatment protocol for daratumumab patients in a large tertiary care hospital provides gateway for implementation in smaller community hospitals.

BACKGROUND: Treatment of multiple myeloma with daratumumab (DARA) is increasing fast. Unfortunately, this antibody also attaches to red blood cells (RBCs) and mimics an autoantibody's panreactivity during pre-transfusion testing, necessitating specialized techniques, (e.g. dithiothreitol (DTT)) for alloantibody detection. Many hospitals use a reference lab for such testing, increasing both cost and turn-around time (TAT). Herein, we compare the cost and TAT, pre and post-implementation of an in-house DTT protocol. METHODS: We designed a validation of our in-house DTT protocol from Nov to Dec 2017 with full implementation on January 1, 2018. We retrospectively reviewed all pre-transfusion tests on DARA patients from Feb 2016 to April 2018, pre and post-implementation of in-house DTT testing. Descriptive statistics were used for patient demographics and a Student t-test was used to compare cost and TATs (pre and post-implementation). RESULTS: We identified 49 patients on DARA treatment requiring transfusion. Samples from these patients were sent to the reference lab 104 times and were tested in-house 28 times. The average TAT for the reference lab was 19h25 m compared to our in-house TAT of 5h9m (an average time-savings of 14h16 m). We spent approximately $33,800 ($325 per test) for 104 reference lab samples versus $806.12 (˜$28.79 per test) for in-house testing of 28 samples. CONCLUSION: We provide an easily implementable DTT protocol for pre-transfusion testing community hospitals and beyond. As more monoclonal antibodies are developed and approved for clinical use, the lessons learned with DARA will expand to deal with interference from future targeted therapies.

Integrated mRNA and miRNA profiling revealed deregulation of cellular stress response in bone marrow mesenchymal stem cells derived from patients with immune thrombocytopenia.

Our understanding of the pathogenesis of immune thrombocytopenia (ITP) remains limited due to the complexity and heterogeneity of the disease. Recently, we observed that bone marrow mesenchymal stem cells (MSCs) derived from ITP patients exhibited growth defects and functional abnormalities that might be involved in the breakdown of self-tolerance. However, the underlying mechanism remains unclear. In this study, we profiled the expression of both mRNAs and miRNAs by utilizing the microarray technique and deciphered the mechanism underlying the impairment of MSCs derived from ITP patients (MSC-ITP). In total, we identified 740 genes and 32 miRNAs that were differentially expressed between ITP patients and controls. A compromised unfolded protein response (UPR) and decreased DNA transcription were shown to be significantly related to MSC-ITP. The interaction of miRNA with mRNA suggested that the cellular stress response, the UPR, and DNA transcription may be involved in the defects observed in MSC-ITP. Key differentially expressed genes were further validated by RT-PCR. Our results highlight that defects in the cellular stress response, as shown by a compromised UPR and differential DNA transcription, play key roles in causing the abnormalities observed in MSC-ITP. These data might contribute to a better understanding of the abnormal bone marrow niche and provide new insights into the pathogenesis of ITP.

Atmospheric chemistry of CH3CHO: the hydrolysis of CH3CHO catalyzed by H2SO4.

Elucidating atmospheric oxidation mechanisms and the reaction kinetics of atmospheric compounds is of great importance and necessary for atmospheric modeling and the understanding of the formation of atmospheric organic aerosols. While the hydrolysis of aldehydes has been detected in the presence of sulfuric acid, the reaction mechanism and kinetics remain unclear. Herein, we use electronic structure methods with CCSD(T)/CBS accuracy and canonical variational transition state theory combined with small-curvature tunneling to study the reaction mechanism and kinetics of the hydrolysis of CH3CHO. The calculated results show that the hydrolysis of CH3CHO needs to overcome an energy barrier of 37.21 kcal mol-1, while the energy barrier is decreased to -9.79 kcal mol-1 with a sulfuric acid catalyst. In addition, the calculated kinetic results show that the H2SO4H2O + CH3CHO reaction is faster than H2SO4 + CH3CHOH2O. Additionally, the H2SO4H2O + CH3CHO reaction can play an important role in the sink of CH3CHO below 260 K occurring during the night period when OH, H2SO4, and H2O concentrations are 104, 108, and 1017 molecules cm-3, respectively, because it can compete well with the CH3CHO + OH reaction. There are wide implications in atmospheric chemistry from these findings because of the potential importance of the catalytic effect of H2SO4 on the hydrolysis of CH3CHO in the atmosphere and in the formation of secondary organic aerosols.

ADAMTS13 and its variants promote angiogenesis via upregulation of VEGF and VEGFR2.

Severe plasma ADAMTS13 deficiency results in the clinical disorder thrombotic thrombocytopenic purpura. However, other potential pathophysiological roles of ADAMTS13 in endothelial cell biology remain unexplored. The goals of this study were to understand the angiogenic pathways ADAMTS13 activates and to identify the important structural components of ADAMTS13 that stimulate angiogenesis. Incubation of human umbilical vein endothelial cells (HUVEC) with 150 ng/mL (1 nM) of recombinant human ADAMTS13 induced VEGF expression by 53 % and increased VEGF mRNA by over sixfold, both within 10 min; the measured VEGF levels steadily decreased over 2 h, as shown by Western blot and ELISA. Phosphorylation of VEGFR2 was significantly enhanced in HUVEC after incubation with ADAMTS13 (1 nM). Structure-function analysis showed that an ADAMTS13 variant containing thrombospondin type 1 (TSP1) 2-8 repeats (TSP1 2-8), TSP1 2-8 plus CUB domains (TSP1 2-8 plus CUB), or TSP1 5-8 repeats plus CUB domains (TSP1 5-8 plus CUB) increased HUVEC proliferation by 41-54 % as compared to the EBM-2 controls. Chemotaxis assays further demonstrated that the TSP1 domains of ADAMTS13 increased HUVEC migration by 2.65-fold. Incubation of HUVEC with both ADAMTS13 variants containing TSP1 repeats and anti-VEGF IgG abrogated the enhanced effect of ADAMTS13 on proliferation, migration, and VEGFR2 phosphorylation. In conclusion, ADAMTS13-induced endothelial cell angiogenesis occurs via the upregulation of VEGF and phosphorylation of VEGFR2. This angiogenic activity depends on the C-terminal TSP1 repeats of ADAMTS13.

The aflatoxin-detoxifizyme specific expression in mouse parotid gland.

The aflatoxin-detoxifizyme (ADTZ) gene derived from Armillariella tabescens was cloned into parotid gland-specific expression vector (pPSPBGPneo) to construct the parotid gland-specific vector expressing ADTZ (pPSPBGPneo-ADTZ). Transgenic mice were generated by microinjection and identified by using PCR and Southern blotting analysis. PCR and Southern blotting analysis showed that total six transgenic mice carried the ADTZ gene were generated. RT-PCR analysis indicated that the expression of ADTZ mRNA could be detected only in parotid glands of the transgenic mice. The ADTZ activity in the saliva was found to be 3.72 ± 1.64 U/mL. After feeding a diet containing aflatoxin B1 (AFB1) for 14 days, the effect of ADTZ on serum biochemical indexes and AFB1 residues in serum and liver of mice were evaluated. The results showed that total protein and globulin contents in the test treatment (transgenic mice) produced ADTZ were significantly higher than that of the positive control, while alanine aminotransferase and aspartate aminotransferase activity in serum of the test treatment (transgenic mice) were remarkably lower compared to that of the positive control (P < 0.05). Moreover, AFB1 residues in serum and liver of the test treatment (transgenic mice) were significantly lower compared with that of the positive control (P < 0.05). These results in the study confirmed that ADTZ produced in transgenic mice could reduce, even eliminate the negative effects of AFB1 on mice.

[Determination of benzyl glucosinolate in Lepidium meyenii from different regions by HPLC].

The content of benzyl isothiocyanate (BITC) which as the enzymatic hydrolysis product of benzyl glucosinolate through thioglucosidase was determined by HPLC. The content of benzyl isothiocyanate (BITC) which as the enzymatic hydrolysis product of benzyl glucosinolate through thioglucosidase was determined by HPLC. The chromatography condition was as follows: Kaseisorb LC ODS 2000 (4.6 mm x 150 mm, 5 min) column with the mobile phase of acetonitrile(A)-water( B) under gradient elution (0-5 min, 3%-8% A; 5-9 min, 8%-48% A; 9-23 min, 48%-62% A; 23-28 min, 62%-99% A); the flow rate was 1.0 mL x min(-1) with 10 microL injection volume; detection wavelength was 246 nm and temperature of column was 40 degrees C. The content of benzyl glucosinolate was in the range of 10.76-17.91 g x L(-1). The method is simple, accurate and good reproducibility which can be used for the determination of benzyl glucosinolate in Lepidium meyenii, effectively.

[Study on the frontier orbital and Raman spectra of Aflatoxin B1 and isomer].

Through computation, this paper obtained Aflatoxin B1 and its trans-isomer molecules stable structure which was rarely reported by the density functional theory(DFT) with B3LYP complex function and 6-311 + g(d, p) basis set. Through a single point calculations and geometry analysis, we know that the cis-structure is more stable than trans-structure. On the basis of this, Raman spectra of two molecules are calculated by the same method and basis set. compared with the Aflatoxin B1 cis-structure powder experimental Raman spectra, it was informed that numerical results with experimental results combined with a better. While 1582, 3065, 1626 means to take the strongest of the three peaks of cis-structure raman characteristics, 1616, 3065, 1659 cm(-1) is indicated for the strongest of the three peaks of trans-structure raman characteristics. Use the Hirshfeld atom division method combined with Multiwfn software to analyze the composition of frontier orbital based on optimization calculation, and it was informed that the electrophilic ability of two monlecules was stronger than the nucleophilic ability. The proportion of C1 atoms in LUMO orbital are respectively 21.48 percent, 20.62 percent by calculating, thus it is predicted that C1 atom is most main position spot depriving of the electronic in DNA to cause cancer. The above-mentioned research has certain theoretical directive significance in detection, transformation and toxicity inhibition of the cis-trans isomers.

Large-Scale Glass-Transition Temperature Prediction with an Equivariant Neural Network for Screening Polymers.

The practically infinite chemical and morphological space of polymers makes them pervasive with applications in materials science but challenges the rational discovery of new materials with favorable properties. Polymer informatics aims to accelerate materials design through property prediction and large-scale virtual screening. In this study, a new method (Lieconv-Tg) has been developed to predict glass-transition temperature (Tg) values from repeating units of polymers based on Lieconv, which is equivariant with transformations from any specified Lie group. The introduction of equivariance allows the prediction of molecular properties from their 3D structures, independent of orientation and position. A total of 27,659 homopolymers with Tg values were collected from PolyInfo, and a standard data set containing 7166 polymers (named data set_Tg) was created for training a robust Lieconv-Tg model. Using the 3D coordinates as input, Lieconv-Tg performs better than Edge-Conditioned Convolution (ECC), and the mean absolute error (MAE) is significantly reduced by ∼6 from ∼30 to ∼24 on both the validation set and the test set, and the R2 value for both the validation set and the test set can reach 0.90. Lieconv-Tg is thus used to screen promising candidates from a benchmark database named PI1M with 995,800 generated polymers. However, there are some implausible repeating units in PI1M. To get more reasonable candidates from PI1M, a new filtering method has been accomplished by utilizing Morgan fingerprints at the polymerization points (MF@PP) of repeating units in data set_Tg. The combination of a standard data set, Lieconv-Tg, and a more reasonable screening strategy provides new directions in materials design for polymers.

Size effects and electronic properties of zinc-doped boron clusters Zn B n (n = 1-15).

CONTEXT: To gain a deeper understanding of zinc-doped boron clusters, theoretical calculations were performed to investigate the size effects and electronic properties of zinc-doped boron clusters. The study of the electronic properties, spectral characteristics, and geometric structures of Zn B n (n = 1-15) is of great significance in the fields of semiconductor materials science, material detection, and improving catalytic efficiency. The results indicate that Zn B n (n = 1-15) clusters predominantly exhibit planar or quasi-planar structures, with the Zn atom positioned in the outer regions of the B n framework. The second stable structure of Zn B 3 is a three-dimensional configuration, indicating that the structures of zinc-doped boron clusters begin to convert from the planar or quasi-planar structures to the 3D configurations. The second low-energy structure of Zn B 15 is a novel configuration. Relative stability analyses show that the Zn B 12 has better chemical stability than other clusters with a HOMO-LUMO gap of 2.79 eV. Electric charge analysis shows that part electrons on zinc atoms are transferred to boron atoms, and electrons prefer to cluster near the B n framework. According to the electron localization function, it gets harder to localize electrons as the equivalent face value drops, and it's challenging to see covalent bond formation between zinc and boron atoms. The spectrograms of Zn B n (n = 1-15) exhibit distinct properties and notable spectral features, which can be used as a theoretical basis for the identification and confirmation of boron clusters doped with single-atom transition metals. METHODS: The calculations were performed using the ABCluster global search technique combined with density functional theory (DFT) methods. The selected low-energy structures were subjected to geometric optimization and frequency calculations at the PBE0/6-311 + G(d) level to ensure structural stability and eliminate any imaginary frequencies. To acquire more precise relative energies, we performed single-point energies calculations for the low-lying isomers of Zn B n (n = 1-15) at the CCSD(T)/6-311 + G(d)//PBE0/6-311 + G(d) level of theory. All calculations were performed using Gaussian 09 software. To facilitate analysis, we utilized software tools such as Multiwfn, and VMD.

Mortality in patients admitted to hospital with heart failure in China: a nationwide Cardiovascular Association Database-Heart Failure Centre Registry cohort study.

BACKGROUND: China has the largest burden of heart failure worldwide. However, large-scale studies on heart failure mortality are scarce. We aimed to investigate mortality and identify risk factors for mortality among patients with heart failure in China. METHODS: This prospective cohort study used data from the China Cardiovascular Association (CCA) Database-Heart Failure Centre Registry, which were linked to the National Mortality Registration Information Management System by the Chinese Centre for Disease Control and Prevention. We included patients enrolled from Jan 1, 2017, to Dec 31, 2021, across 572 CCA Database-Heart Failure Centre certified hospitals in 31 provinces of mainland China. Eligible patients were aged 18 years or older (younger than 100 years) with a principal discharge diagnosis of heart failure based on Chinese heart failure guidelines. All-cause mortality at 30 days, 1 year, and 3 years for patients with heart failure were calculated and the causes of death were recorded. Multivariable analysis was used to analyse factors associated with all-cause mortality and cardiovascular mortality. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2200066305. FINDINGS: Of the 327 477 patients in the registry, 230 637 eligible adults with heart failure were included in our analyses. Participant mean age was 69·3 years (SD 13·2), 94 693 (41·1%) participants were female, and 135 944 (58·9%) were male. The median follow-up time was 531 days (IQR 251-883). Post-discharge all-cause mortality of patients with heart failure at 30 days was 2·4% (95% CI 2·3-2·5), at 1 year was 13·7% (13·5-13·9), and at 3 years was 28·2% (27·7-28·6). Cardiovascular death accounted for 32 906 (71·5%) of 46 006 all-cause deaths. Patients with heart failure with reduced ejection fraction had the highest all-cause mortality. A lower guideline adherence score was independently associated with the increase of all-cause and cardiovascular mortality. INTERPRETATION: In China, mortality for patients with heart failure is still high, especially in patients with reduced ejection fraction. Our findings suggest that guideline-directed medical therapy needs to be improved. FUNDING: National High Level Hospital Clinical Research Funding, the Capital's Funds for Health Improvement and Research, and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Cd2+ as a Ca2+ surrogate in protein-membrane interactions: isostructural but not isofunctional.

Due to its favorable spectroscopic properties, Cd(2+) is frequently used as a probe of Ca(2+) sites in proteins. We investigate the ability of Cd(2+) to act as a structural and functional surrogate of Ca(2+) in protein-membrane interactions. C2 domain from protein kinase Cα (C2α) was chosen as a paradigm for the Ca(2+)-dependent phosphatidylserine-binding peripheral membrane domains. We identified the Cd(2+)-binding sites of C2α using NMR spectroscopy, determined the 1.6 Å crystal structure of Cd(2+)-bound C2α, and characterized metal-ion-dependent interactions between C2α and phospholipid membranes using fluorescence spectroscopy and ultracentrifugation experiments. We show that Cd(2+) forms a tight complex with the membrane-binding loops of C2α but is unable to support its membrane-binding function. This is in sharp contrast with Pb(2+), which is almost as effective as Ca(2+) in driving the C2α-membrane association process. Our results provide the first direct evidence for the specific role of divalent metal ions in mediating protein-membrane interactions, have important implications for metal substitution studies in proteins, and illustrate the potential diversity of functional responses caused by toxic metal ions.