Interchain-expanded extra-large-pore zeolites.

Stable aluminosilicate zeolites with extra-large pores that are open through rings of more than 12 tetrahedra could be used to process molecules larger than those currently manageable in zeolite materials. However, until very recently1-3, they proved elusive. In analogy to the interlayer expansion of layered zeolite precursors4,5, we report a strategy that yields thermally and hydrothermally stable silicates by expansion of a one-dimensional silicate chain with an intercalated silylating agent that separates and connects the chains. As a result, zeolites with extra-large pores delimited by 20, 16 and 16 Si tetrahedra along the three crystallographic directions are obtained. The as-made interchain-expanded zeolite contains dangling Si-CH3 groups that, by calcination, connect to each other, resulting in a true, fully connected (except possible defects) three-dimensional zeolite framework with a very low density. Additionally, it features triple four-ring units not seen before in any type of zeolite. The silicate expansion-condensation approach we report may be amenable to further extra-large-pore zeolite formation. Ti can be introduced in this zeolite, leading to a catalyst that is active in liquid-phase alkene oxidations involving bulky molecules, which shows promise in the industrially relevant clean production of propylene oxide using cumene hydroperoxide as an oxidant.

Identification of vital chemical information via visualization of graph neural networks.

Qualitative or quantitative prediction models of structure-activity relationships based on graph neural networks (GNNs) are prevalent in drug discovery applications and commonly have excellently predictive power. However, the network information flows of GNNs are highly complex and accompanied by poor interpretability. Unfortunately, there are relatively less studies on GNN attributions, and their developments in drug research are still at the early stages. In this work, we adopted several advanced attribution techniques for different GNN frameworks and applied them to explain multiple drug molecule property prediction tasks, enabling the identification and visualization of vital chemical information in the networks. Additionally, we evaluated them quantitatively with attribution metrics such as accuracy, sparsity, fidelity and infidelity, stability and sensitivity; discussed their applicability and limitations; and provided an open-source benchmark platform for researchers. The results showed that all attribution techniques were effective, while those directly related to the predicted labels, such as integrated gradient, preferred to have better attribution performance. These attribution techniques we have implemented could be directly used for the vast majority of chemical GNN interpretation tasks.

HOXB9 promotes laryngeal squamous cell carcinoma progression by upregulating MMP12.

Transcriptional factor HOXB9, a part of the HOX gene family, plays a crucial role in the development of diverse cancer types. This study aimed to elucidate the regulatory mechanism of HOXB9 on the proliferation and invasion of laryngeal squamous cell carcinoma (LSCC) cells to provide guidance for the development and prognosis of LSCC. The CRISPR/Cas9 method was employed in LSCC cell lines to knock out the HOXB9 gene and validate its effects on the proliferation, migration, invasion, and regulation of LSCC cells. CCK-8 and flow cytometry were used to detect cell viability and proliferation; Tunnel was used to detect cell apoptosis, and transwell was used to detect cell migration and invasion. The effect of HOXB9 on tumor growth was tested in nude mice. The downstream target genes regulated by HOXB9 were screened by microarray analysis and verified by Western blotting, immunohistochemistry, chromatin immunoprecipitation, and double-luciferase reporter assays. The current research investigated molecular pathways governed by HOXB9 in the development of LSCC. Additionally, both laboratory- and living-organism-based investigations revealed that disrupting the HOXB9 gene through the CRISPR/CAS9 mechanism restrained cellular growth, movement, and infiltration, while enhancing cellular apoptosis. Detailed analyses of LSCC cell strains and human LSCC samples revealed that HOXB9 promoted LSCC progression by directly elevating the transcriptional activity of MMP12. HOXB9 could influence changes in LSCC cell functions, and the mechanism of action might be exerted through its downstream target gene, MMP12.

Fast-Crosslinking Enabled Self-Roughed Polydimethylsiloxane Transparent Superhydrophobic Coating and Its Application in Anti-Liquid-Interference Electrothermal Device.

Polydimethylsiloxane (PDMS)-based transparent and superhydrophobic coatings have important applications, such as anti-icing, corrosion resistance, self-cleaning, etc. However, their applications are limited by the inevitable introduction of nanoparticles/high-temperature/segmented PDMS to facilitate a raspy surface. In this study, a self-roughed, neat PDMS superhydrophobic coating with high transparency is developed via a one-step spray-coating technique. PDMS suspensions with various droplet sizes are synthesized and used as building blocks for raspy surface formation by controlled curing on the warm substrate. The optimal coating exhibits a large water contact angle of 155.4° and transparency (T550 = 82.3%). Meanwhile, the employed spray-coating technique is applicable to modify a plethora of substrates. For proof-of-concept demonstrations, the use of the PDMS hydrophobic coating for anti-liquid-interference electrothermal devices and further transparent observation window for long-term operation in a sub-zero environment is shown successful. The proposed facile synthesis method of hydrophobic PDMS coating is expected to have great potential for a broad range of applications in the large-scale fabrication of fluorine-free, eco-friendly superhydrophobic surfaces.

In-Depth Understanding of the Oxidative Compatibility of Volatile Organic Compounds with Mn2O3 and Pt-Loaded Catalysts.

Designing suitable catalysts for efficiently degrading volatile organic compounds (VOCs) is a great challenge due to the distinct variety and nature of VOCs. Herein, the suitability of different typical VOCs (toluene and acetone) over Pt-based catalysts and Mn2O3 was investigated carefully. The activity of Mn2O3 was inferior to Pt-loaded catalysts in toluene oxidation but showed superior ability for destroying acetone, while Pt loading could boost the catalytic activity of Mn2O3 for both acetone and toluene. This suitability could be determined by the physicochemical properties of the catalysts and the structure of the VOC since toluene destruction activity is highly reliant on Pt0 in the metallic state and linearly correlated with the amount of surface reactive oxygen species (Oads), while the crucial factor that affects acetone oxidation is the mobility of lattice oxygen (Olat). The Pt/Mn2O3 catalyst shows highly active Pt-O-Mn interfacial sites, favoring the generation of Oads and promoting Mn-Olat mobility, leading to its excellent performance. Therefore, the design of abundant active sites is an effective means of developing highly adaptive catalysts for the oxidation of different VOCs.

Identification and treatment of persistent small airway dysfunction in paediatric patients with asthma: a retrospective cohort study.

BACKGROUND: Asthma is a common respiratory disease. In asthma, the small airways have more intensive inflammation and prominent airway remodelling, compared to the central airways. We aimed to investigate the predictive value of risk factors and the fractional concentration of exhaled nitric oxide (FeNO) for persistent small airway dysfunction (p-SAD), and compare the effects of different treatment modalities. METHODS: This retrospective cohort study included 248 children with asthma (aged 4-11 years). Binary logistic regression was used to analyse the risk factors for p-SAD. Correlations among FEV1/FVC, small airway function parameters, and FeNO levels in patients with asthma were analysed using Spearman's rank correlation. The receiver operating characteristic curve and the Delong test were used to analyse the predictive value of FeNO for p-SAD. Differences in the treatment effects of inhaled corticosteroids (ICS) and ICS with a long-acting beta-agonist (ICS/LABA) on p-SAD were analysed using Fisher's exact test. RESULTS: Asthmatic children with older age of receiving the regular treatment (OR 1.782, 95% CI 1.082-2.935), with younger age at the time of onset of suspected asthma symptoms (OR 0.602, 95% CI 0.365-0.993), with longer duration of using ICS or ICS/LABA (OR 1.642, 95% CI 1.170-2.305) and with worse asthma control (OR 3.893, 95% CI 1.699-8.922) had increased risk for p-SAD. Significant negative correlations of small airway function parameters with FeNO at a 200 mL/s flow rate (FeNO200), and the concentration of nitric oxide in the alveolar or acinar region (CaNO) were observed. The areas under the curve of FeNO200 (cut-off:10.5ppb), CaNO (cut-off:5.1ppb), and FeNO200 combined with CaNO were 0.743, 0.697, and 0.750, respectively, for asthma with p-SAD. After using ICS or ICS/LABA, switching to ICS/LABA was easier than continuing with ICS to improve small airway dysfunction (SAD) in the 8th month. CONCLUSIONS: Paediatric asthma with p-SAD is associated with older age at receiving regular treatment, younger age at the time of onset of suspected asthma symptoms, longer duration of using ICS or ICS/LABA, worse asthma control, and higher FeNO200 and CaNO levels, all of which can be combined with small airway function indicators to distinguish p-SAD from asthma. ICS/LABA improves SAD better than ICS alone.

Metformin Protects Against Acute Kidney Injury Induced by Lipopolysaccharide via Up-Regulating the MCPIP1/SIRT1 Pathway.

In the present study, we aimed to explore the effect and underlying mechanism of metformin on lipopolysaccharide (LPS)-induced acute kidney injury (AKI). A total of 24 BALB/C mice were randomly divided into four groups: control group, LPS group and metformin group (50 or 100 mg/kg). The histological changes and cell apoptosis in kidney tissues were detected by hematoxylin-eosin staining and terminal-deoxynucleotidyl transferase-mediated nick end labeling assay, respectively. Enzyme-linked immunosorbent assay was applied to determine serum levels of blood urea nitrogen (BUN), kidney injury molecule-1 (Kim-1), creatinine (Cre), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß). Western blotting analysis were carried out to confirm the expressions of monocyte chemotactic protein-inducible protein 1 (MCPIP1), silent information regulator sirtuin 1 (SIRT1), and NF-κB p65 (acetyl K310). Compared with the control group, the mice in LPS group had glomerular capillary dilatation, renal interstitial edema, tubular cell damage and apoptosis. The serum levels of BUN, KIM-1, Cre, TNF-α, and IL-1ß in LPS group were significantly higher than those in control group. Moreover, LPS also elevated the expressions of MCPIP1 and NF-κB p65 (acetyl K310) but decreased the expression of SIRT1 in kidney tissues. However, metformin distinctly decreased LPS-induced renal dysfunction, the serum levels of BUN, KIM-1, Cre, TNF-α, and IL-1ß. In addition, metformin markedly increased the expressions of MCPIP1 and SIRT1 but decreased the expression of NF-κB p65 (acetyl K310) in kidney tissues. Metformin prevented LPS-induced AKI by up-regulating the MCPIP1/SIRT1 signaling pathway and subsequently inhibiting NF-κB-mediated inflammation response.

High incidence of EDNRB gene mutation in seven southern Chinese familial cases with Hirschsprung's disease.

PURPOSE: Hirschsprung's disease (HSCR) is the leading cause of neonatal functional intestinal obstruction, which has been identified in many familial cases. HSCR, a multifactorial disorder of enteric nervous system (ENS) development, is associated with at least 24 genes and seven chromosomal loci, with RET and EDNRB as its major genes. We present a genetic investigation of familial HSCR to clarify the genotype-phenotype relationship. METHODS: We performed whole exome sequencing (WES) on Illumina HiSeq X Ten platform to investigate genetic backgrounds of core family members, and identified the possibly harmful mutation genes. Mutation carriers and pedigree relatives were validated by Sanger sequencing for evaluating the gene penetrance. RESULTS: Four familial cases showed potential disease-relative variants in EDNRB and RET gene, accounting for all detection rate of 57.1%. Three familial cases exhibited strong pathogenic variants as frameshift or missense mutations in EDNRB gene. A novel c.367delinsTT mutation of EDNRB was identified in one family member. The other two EDNRB mutations, c.553G>A in family 2 and c.877delinsTT in family 5, have been reported in previous literatures. The penetrance of EDNRB variants was 33-50% according mutation carries. In family 6, the RET c.1858T>C (C620R) point mutation has previously been reported to cause HSCR, with 28.5% penetrance. CONCLUSION: We identified a novel EDNRB (deleted C and inserted TT) mutation in this study using WES. Heterozygote variations in EDNRB gene were significantly enriched in three families and RET mutations were identified in one family. EDNRB variants showed an overall higher incidence and penetrance than RET in southern Chinese families cases.

Clinical Assessment of Magnetic Resonance Spectroscopy and Diffusion-Weighted Imaging in Diffuse Glioma: Insights Into Histological Grading and IDH Classification.

PURPOSE: To assess the diagnostic utility of clinical magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI) in distinguishing between histological grading and isocitrate dehydrogenase (IDH) classification in adult diffuse gliomas. METHODS: A retrospective analysis was conducted on 247 patients diagnosed with adult diffuse glioma. Experienced radiologists evaluated DWI and MRS images. The Kruskal-Wallis test examined differences in DWI and MRS-related parameters across histological grades, while the Mann-Whitney U test assessed molecular classification. Receiver Operating Characteristic (ROC) curves evaluated parameter effectiveness. Survival curves, stratified by histological grade and IDH classification, were constructed using the Kaplan-Meier test. RESULTS: The cohort comprised 141 males and 106 females, with ages ranging from 19 to 85 years. The Kruskal-Wallis test revealed significant differences in ADC mean, Cho/NAA, and Cho/Cr concerning glioma histological grade (P < .01). Subsequent application of Dunn's test showed significant differences in ADC mean among each histological grade (P < .01). Notably, Cho/NAA exhibited a marked distinction between grade 2 and grade 3/4 gliomas (P < .01). The Mann-Whitney U test indicated that only ADC mean showed statistical significance for IDH molecular classification (P < .01). ROC curves were constructed to demonstrate the effectiveness of the specified parameters. Survival curves were also delineated to portray survival outcomes categorized by histological grade and IDH classification. Conclusions: Clinical MRS demonstrates efficacy in glioma histological grading but faces challenges in IDH classification. Clinical DWI's ADC mean parameter shows significant distinctions in both histological grade and IDH classification.

Effects of receptor properties on particle internalization through receptor-mediated endocytosis.

Receptor-mediated endocytosis (RME) is a highly complex process carried out by bioparticles, such as viruses and drug carriers, to enter cells. The discovery of both clathrin-dependent and clathrin-free pathways makes the RME process even more intriguing. Numerical models have been developed to facilitate the exploration of the process. However, the impacts of the receptor properties on RME have been less studied partially due to the oversimplifications of the receptor models. In this paper, we implement a stochastic model to systematically investigate the effects of mechanical (receptor flexure), geometrical (receptor length) and biochemical (ligand-receptor cutoff) properties of receptors, on RME with and without the existence of clathrin. Our simulation results show that the receptor's flexural rigidity plays an important role in RME with clathrin. There is a threshold beyond which particle internalization will not occur. Without clathrin, it is very difficult to achieve complete endocytosis with ligand-receptor interactions alone. A shorter receptor length and longer ligand-receptor reaction cutoff promote the formation of ligand-receptor bonds and facilitate particle internalization. Complete internalization can only be obtained with an extremely short receptor length and long reaction cutoff. Therefore, there are most likely some additional mechanisms to drive the membrane deformation in clathrin-free RME. Our results yield important fundamental insights into RME and provide crucial guidance when correlating the simulation results with experimental observations.

Effective Toluene Ozonation over δ-MnO2: Oxygen Vacancy-Induced Reactive Oxygen Species.

To improve the reactivity and lifetime of catalysts in the catalytic ozonation of toluene, a simple strategy was provided to regulate the morphology and microstructure of δ-MnO2 via the hydrothermal reaction temperature. The effects of the reaction temperature and the ozone to toluene concentration ratio on the catalyst performance were investigated. The optimized MnO2-260 catalyst prepared at the limiting hydrothermal temperature (260 °C) showed high catalytic activity (XTol = 95%) and excellent stability (1200 min) at the approximately ambient temperature of 40 °C, which was superior to the results in previous studies. The structure and morphology of δ-MnO2 were characterized by extended X-ray absorption fine structure, X-ray diffraction, scanning electron microscopy, positron annihilation lifetime spectroscopy, electron spin resonance, and other techniques. Experimental results and density functional theory calculations were in agreement that surface oxygen vacancy clusters, especially surface oxygen dimer vacancies, are critical in ozone activation. Oxygen vacancies can facilitate the adsorption and activation of O3 to generate reactive oxygen species (ROS, including 1O2, O2-, and •OH), leading to superior ozonation activity to degrade toluene and intermediates. Meanwhile, free radical detection and scavenger tests indicated that •OH is the primary ROS during toluene ozonation rather than 1O2 or O2-.

Synergistic Catalytic Oxidation of Typical Volatile Organic Compound Mixtures on Mn-Based Catalysts: Significant Promotion Effect and Reaction Mechanism.

The miscellaneous volatile organic compounds (VOCs) in industrial flue gas streams usually demonstrate significant mutual inhibition effects, and the behavior of a particular VOC in mixtures is not clear, which hinders the application of catalytic technology. This study examines the catalytic oxidation and mixing effects of representative VOCs in industrial exhausts, consisting of acetone (AC), ethyl acetate (EA), and toluene (Tol), on common Mn-based catalysts (e.g., MnO2, Mn2O3, LaMnO3, and Mn3O4) by means of intrinsic activity evaluation, coadsorption, VOC temperature-programmed oxidation, in situ diffuse reflectance infrared Fourier transform spectroscopy, and gas chromatography-mass spectrometry. The results showed no inhibiting effect on the conversion of these VOCs when combusted together; instead, a significant mutual promotion effect was found, especially on Tol destruction, with a sharp decrease in the Tol T50 from 214 to 158 °C on MnO2. It is proposed for the first time that the addition of AC/EA in Tol combustion leads to the generation of o/m-methyl phenol, which changes the rate-determining step of the ring-opening process, thus elevating the conversion of Tol together with AC and EA in the mixture at low temperatures.

Whole fresh fruit intake and risk of incident diabetes in different glycemic stages: a nationwide prospective cohort investigation.

PURPOSE: Fruit intake is beneficial to several chronic diseases, but controversial in diabetes. We aimed to investigate prospectively the associations of whole fresh fruit intake with risk of incident type 2 diabetes (T2D) in subjects with different glucose regulation capacities. METHODS: The present study included 79,922 non-diabetic participants aged ≥ 40 years from an ongoing nationwide prospective cohort in China. Baseline fruit intake information was collected by a validated food frequency questionnaire. Plasma HbA1c, fasting and 2 h post-loading glucose levels were measured at both baseline and follow-up examinations. Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for incident diabetes among participants with normal glucose tolerance (NGT) and prediabetes, after adjusted for multiple confounders. Restricted cubic spline analysis was applied for dose-response relation. RESULTS: During a median 3.8-year follow-up, 5886 (7.36%) participants developed diabetes. Overall, we identified a linear and dose-dependent inverse association between dietary whole fresh fruit intake and risk of incident T2D. Each 100 g/d higher fruit intake was associated with 2.8% lower risk of diabetes (HR 0.972, 95%CI [0.949-0.996], P = 0.0217), majorly benefiting NGT subjects with 15.2% lower risk (HR 0.848, 95%CI [0.766-0.940], P = 0.0017), while not significant in prediabetes (HR 0.981, 95%CI 0.957-4.005, P = 0.1268). Similarly, the inverse association was present in normoglycemia individuals with a 48.6% lower risk of diabetes when consuming fruits > 7 times/week comparing to those < 1 time/week (HR 0.514, 95% CI [0.368-0.948]), but not in prediabetes (HR 0.883, 95% CI [0.762-1.023]). CONCLUSION: These findings suggest that higher frequency and amount of fresh fruit intake may protect against incident T2D, especially in NGT, but not in prediabetes, highlighting the dietary recommendation of higher fresh fruit consumption to prevent T2D in normoglycemia population.

Septin9 DNA methylation as a promising biomarker for cervical cancer.

Aberrant Septin9 methylation in cervical cancer has been rarely studied. We aimed to identify its diagnostic value in cervical cancer using cervical scrapings, and its predictive potential in plasma for pelvic nodal metastasis of cervical cancer. The statuses of methylated Septin9 in fresh cervical lesions and cervical scrapings were first evaluated by using quantitative methylation-specific PCR. Subsequently, the relationship between Septin9 methylation in 113 plasma samples and pelvic nodal metastasis of cervical cancer was evaluated. Methylated Septin9 was detected in all cancerous tissues, but not in cervicitis. The degrees of Septin9 methylation increased with growing severity of cervical lesions in cervical scrapings. The sensitivity of methylated Septin9 was lower than that of cytology, while it yielded a high specificity and area under the curve in detecting high-grade squamous intraepithelial lesion or cervical cancer; and when Septin9 methylation combined with HPV16/18 genotyping, the sensitivity would increase from 70.42% to 82.39%. Plasma-based Septin9 methylation had a high discriminatory power in predicting pelvic nodal metastasis of cervical cancer, with an optimal specificity of 81.48%. In conclusion, we demonstrated methylated Septin9 to be an innovative diagnostic biomarker for cervical cancer and its non-invasive predictive potential in plasma for pelvic nodal metastasis of cervical cancer.Impact statementWhat is already known on this subject? The occurrence of cervical cancer is related to Septin9 methylation. In fresh specimens and cervical scrapings, we found the degrees of methylated Septin9 increased with growing severity of cervical lesions. Compared with HPV16/18 genotyping and cytological detection, Septin9 methylation had a better specificity and AUC in detecting ≥ HSIL. Furthermore, plasma-based Septin9 methylation also had a high specificity for pelvic lymphatic metastasis prediction.What the results of this study add? Methylation analysis of Septin9 indicated a similar sensitivity, specificity and AUC in detecting ≥ HSIL, relative to HPV16/18 genotyping. Compared with cytological method, Septin9 methylation also yielded a higher specificity and AUC in detecting ≥ HSIL. And we also found plasma-based Septin9 methylation had a high discriminatory power in predicting pelvic nodal metastasis of cervical cancer, with an optimal specificity of 81.48%; additionally an increasing sensitivity from 50% to nearly 80% was found when combined with SCCAg.What the implications are of these findings for clinical practice and/or further research? This study aimed to evaluate the relationship between Septin9 methylation and cervical cancer, and to explore the value of methylated Septin9 in the detection of cervical (pre)cancerous lesions. Moreover, we would explore plasma-based ctDNA biomarkers for pelvic lymphatic metastasis prediction of cervical cancer, to improve non-invasive predictive accuracy of pelvic nodal metastasis and reduce the complications caused by pelvic lymphadenectomy.

Crack Patterns of Environmental Plastic Fragments.

Secondary microplastics usually come from the breakdown of larger plastics due to weathering and environmental stress cracking of plastic wastes. In the present study, 5013 plastic fragments were collected from coastal beaches, estuary dikes, and lake banks in China. The fragment sizes ranged from 0.2 to 17.1 cm, and the dominant polymers were polypropylene and polyethylene. Cracks were observed on the surfaces of 49-56% of the fragments. Based on the extracted crack images, we proposed a general crack pattern system including four crack types with specific definitions, abbreviations, and symbols. The two-dimensional spectral analysis of the cracks suggests that the first three patterns showed good regularity and supported the rationality of the pattern system. Some crack metrics (e.g., line density) were closely correlated with the carbonyl index and additives (e.g., phthalate esters) of fragments. For crack investigation in field, we proposed a succinct protocol, in which five crack ranks were established to directly characterize the degree of cracking based on the line density values. The system was successfully applied to distinguish the differences in crack features at two representative sites, which indicates that crack pattern is a useful tool to describe the morphological changes of plastic surfaces in the environment.

Therapeutic effects of allopurinol on the function of left ventricular and activity of matrix metalloproteinase enzymes (MMPs) in patients with chronic heart failure.

Heart failure is a growing public health problem, especially in the elderly, often occurring due to ischemia and coronary artery disease. Allopurinol can protect against myocardial ischemia and improve myocardial energy utilization during ischemia. On the other hand, matrix metalloproteinase (MMP) enzymes play an essential role in causing atherosclerosis, obstruction, and myocardial infarction. Therefore, in the present study, the effect of allopurinol on the function of the left ventricular and the activity of MMP-1, MMP-2, MMP-3, and MMP-9 were evaluated in heart failure patients. In this clinical trial, 82 patients were randomly assigned to allopurinol or placebo in addition to standard treatment. Echocardiographic evaluations were performed before treatment and six months after treatment. Also, after allopurinol treatment, plasma and peripheral blood mononuclear cells were extracted from control and intervention groups. The active form of MMPs was measured by ELISA and mRNA expression by Real-time PCR. The rate of change in left ventricular ejection fraction in the allopurinol group was significantly higher than patients in the control group. There was also found more improvement in NYHA class in patients receiving allopurinol than in the control group. ELISA results showed that all plasma MMP levels in the control group were significantly higher than those in the allopurinol group (P<0.001). Quantitative determination of mRNA expression in MMPs by Real-time RT-PCR revealed that, except for MMP-9, there was no significant difference in the expression of evaluated MMPs between the treatment and control groups. In general, the results showed that long-term administration of allopurinol improves left ventricular function, and it has beneficial effects on the life quality of patients with heart failure.

A novel amino acid site of N protein could affect the PRRSV-2 replication by regulating the viral RNA transcription.

BACKGROUND: Finding the key amino acid sites that could affect viral biological properties or protein functions has always been a topic of substantial interest in virology. The nucleocapsid (N) protein is one of the principal proteins of the porcine reproductive and respiratory syndrome virus (PRRSV) and plays a vital role in the virus life cycle. The N protein has only 123 or 128 amino acids, some of key amino acid sites which could affect the protein functions or impair the viral biological characteristics have been identified. In this research, our objective was to find out whether there are other novel amino acid sites of the N protein can affect N protein functions or PRRSV-2 replication. RESULTS: In this study, we found mutated the serine78 and serine 99of the nucleocapsid (N) protein can reduce the N-induced expression of IL-10 mRNA; Then, by using reverse genetics system, we constructed and rescued the mutant viruses, namely, A78 and A99.The IFA result proved that the mutations did not affect the rescue of the PRRSV-2. However, the results of the multistep growth kinetics and qPCR assays indicated that, compared with the viral replication ability, the titres and gRNA levels of A78 were significantly decreased compared with the wild-type. Further study showed that a single amino acid change from serine to alanine at position 78 of the N protein could abrogates the level of viral genomic and subgenomic RNAs. It means the mutation could significant decrease the viral replication efficiency in vitro. CONCLUSIONS: Our results suggest that the serine78 of N protein is a key site which could affect the N protein function and PRRSV replication ability.

Open reduction and locked compression plate fixation, with or without allograft strut, for periprosthetic fractures in patients who had a well-fixed femoral stem: a retrospective study with an average 2-year follow-up.

BACKGROUND: The use of cortical strut allograft has not been determined for Vancouver type B1 or C fracture. This study aimed to evaluate the short-term efficacy of locking compression plating with or without cortical strut allograft in managing these types of fractures. METHODS: We retrospectively assessed 32 patients (17 males, 15 females; 23-88 years, mean: 67.2 years) with Vancouver type B1 or C fractures. Seventeen patients (Group A; B1 fractures in 15 hips, C fractures in 2 hips) were treated with open reduction and internal fixation with locking compression plates (group A). The other 15 patients (Group B; B1 in 14 hips, C in 1 hip) were fixed by locking compression plating combined with cortical strut allografting (group B). The fracture healing rate, healing time, complications and function were compared between these two groups. RESULTS: The mean follow-up time was 32.4 months (12 to 66), and the overall fracture union rate of the 32 patients was 96.9%. Group B had a higher fracture union rate than Group A, but the difference was not statistically significant. Group A had one case of nonunion of type B1 fracture and one case of malunion; the mean time to fracture healing was 5.3 months (3 to 9). In group B, all patients reached bony union without malunion, with a mean time of fracture healing of 5.1 months (3 to 8). CONCLUSION: Treatment of Vancouver type B1 or C fractures by locking compression plating, with or without cortical strut allografting, resulted in similar union rates in these patients. This suggest that, the use of cortical strut allografting should be decided cautiously.

Mitral valve regurgitation is associated with left atrial fibrosis in patients with atrial fibrillation.

BACKGROUND: Low voltage zones (LVZ) are associated with poor outcomes in patients with atrial fibrillation (AF). The APPLE and DR-FLASH scores predict LVZ in patients undergoing catheter ablation. This study aimed to assess the relationship of mitral valve regurgitation (MR) and LVZ after adjusting for APPLE or DR-FLASH scores. METHODS: This was a retrospective study on patients with AF who underwent their first catheter ablation. All patients underwent a transthoracic echocardiographic examination before ablation. The APPLE and DR-FLASH scores were calculated at baseline. LVZ determined by high-density mapping was defined as bipolar voltage amplitude <0.5 mV. LVZ presence was defined as LVZ covering >5% of the left atrial surface area. RESULTS: Altogether, 152 patients (mean age 62.0 ± 10.8 years, 65.8% men, and 36.2% with persistent AF) were included. Of the 152 patients, 47 (30.9%) had LVZ. The patients with LVZ had more moderate-to-severe MR (17.0% vs. 3.8%, P = 0.014) and higher APPLE scores (1.7 ± 1.1 vs. 1.2 ± 1.1, P = 0.009) and DR-FLASH scores (3.0 ± 1.5 vs. 2.4 ± 1.4, P = 0.010). Using multivariate logistic regression analysis, we found moderate-to-severe MR was related to LVZ presence after adjusting for the APPLE (OR 4.040, P = 0.034) or DR-FLASH (OR 4.487, P = 0.020) scores. Furthermore, moderate-to-severe MR had an incremental predictive value for LVZ presence in addition to the APPLE (P = 0.03) or DR-FLASH (P = 0.02) scores. CONCLUSION: In patients with AF, MR severity was related to LVZ after adjusting the APPLE score or DR-FLASH score.

Open access databases available for the pesticide lead discovery.

Pesticide research is a multi-disciplinary collaborative study, and big data analysis based on integrating information from databases benefits decision-making in pesticide research. In the last 40 years, dozens of pesticide-related databases have been built up to describe their biological activities, toxicity, modes of action, and environmental risks, etc. However, these data are scattered and overlapping in different databases in multiple inconsistent formats, which is not convenient for information analysis and comparison. In this study, the content of 26 open access databases related to pesticide research was illustrated according to the information provided for the ligand-based drug design (LBDD) and receptor-based (or structure-based drug design, SBDD), and was summarized into three categories:1) the correspondence between the chemical structures and functional properties (biological activity, resistance, toxicity, environmental adaptation); 2) action mode study (target identification, target structures, and biological pathways); 3) computational servers for pesticide design. To our knowledge, this is the first review about the open access databases for pesticide research. The data classification could facilitate the information accessibility for pesticide research, and speed up the decision-making process in pesticide discovery.