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Abstract: Detailed investigations of microstructural feature, mechanical property, fatigue strength, and damage mechanism were conducted on hybrid laser welded 7020‐T651 aluminum alloys used into high‐speed railway vehicles. The results show that the hybrid laser welding process can induce significant changes of microstructures and alloying elements, together with numerous gas pores. Such local modifications degrade the fatigue performance. The tensile strength of welded joints was approximately 74% with respect to the base metal, thus satisfying the design standard. The fatigue property was determined in the low and high cycle regimes. It was found that the fatigue strength of welded joints was fairly inferior to that of the base metal, but far higher than the IIW recommended value. Furthermore, welding defects were well believed to contribute to the shorter fatigue life. The small fatigue crack growth presented highly discontinuous and inhomogeneous due to microstructure and porosity. By contrast, the crack stable growth stage was less sensitive to microstructural features of hybrid welded joints. [ABSTRACT FROM AUTHOR]

Summary: The interplay between hepatitis B (HBV) and delta (HDV) viruses is complex and not always characterized during chronic HDV infection. We assessed the clinical usefulness of new quantitative assays for HBV and HDV serum markers in a retrospective cross‐sectional study. Sera obtained from 122 HDV genotype 1 and HBV genotype D coinfected, anti‐HIV‐negative patients (71 males; median age 49.8 [21.7‐66.9] years), recruited consecutively in two geographical areas (Italy 69 patients, Romania 53 patients) with different HBV and HDV epidemiology, were tested for HBsAg, HBV‐DNA, HBcrAg, total anti‐HBc, HDV‐RNA, IgM and total anti‐HDV using quantitative assays. Cirrhosis, which showed comparable prevalence in the two cohorts, was diagnosed in 97 of 122 (79.5%) patients. At multivariate analysis, cirrhosis was associated with lower total anti‐HBc/IgM anti‐HDV ratio (OR 0.990, 95% CI 0.981‐0.999, P = .038), whereas disease activity was associated with higher total anti‐HDV (OR 10.105, 95% CI 1.671‐61.107, P = .012) and HDV‐RNA levels (OR 2.366, 95% CI 1.456‐3.844, P = .001). HDV‐RNA serum levels showed a positive correlation with HBV‐DNA (ρ = 0.276, P = .005), HBsAg (ρ = 0.404, P < .001) and HBcrAg (ρ = 0.332, P < .001). The combined quantitative profiling of HBV and HDV serum markers identifies specific patterns associated with activity and stage of chronic hepatitis D (CHD). HDV pathogenicity depends on the underlying active HBV infection in spite of the inhibition of its replication. HDV‐RNA, IgM anti‐HDV, total anti‐HDV, total anti‐HBc, HBsAg and HBcrAg serum levels qualify for prospective studies to predict progressive CHD and identify candidates to antiviral therapy. [ABSTRACT FROM AUTHOR]

Studies regarding the clinical significance of quantitative hepatitis B core antibody (anti-HBc) in patients with chronic hepatitis B receiving first-line nucleos(t)ide analogues is limited. The aim of this study was to determine the performance of anti-HBc as a predictor for hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive CHB patients treated with entecavir. This was a retrospective cohort study consisting of 139 Chinese patients enrolled in a multicenter clinical trial treated with entecavir or entecavir maleate for up to 240 weeks. Anti-HBc evaluation was conducted for all the available samples using a newly developed double-sandwich anti-HBc immunoassay. At week 240, 35 (25.2%) patients achieved a serological response (HBeAg seroconversion) and these patients at week 240 had significantly higher levels of anti-HBc ( P<.01). We defined 4.65 log10 IU·mL−1, with a maximum sum of sensitivity and specificity, as the optimal cut-off value of baseline anti-HBc level to predict seroconversion. Patients with baseline anti-HBc ≥4.65 log10 IU·mL−1 had 28.0% (26/93) and 35.5% (33/93) chance of seroconversion at weeks 144 and 240, respectively. The baseline anti-HBc level was the strongest predictor for seroconversion at week 144 (OR: 5.78, 95% confidence interval [CI]: 2.05-16.34, P=.001). The baseline anti-HBc level was a strong predictor for seroconversion at week 240 (OR: 5.36, 95% CI: 2.17-13.25, P<.001). Hence, baseline anti-HBc titre is a useful predictor of long-term entecavir therapy efficacy in HBeAg-positive CHB patients, which could be used to optimize antiviral therapy. [ABSTRACT FROM AUTHOR]

ABSTRACT The effect of anaerobic hydrolysis of particulate COD (pCOD) on biological phosphorous removal in extended anaerobic condition was investigated through (i) sequencing batch reactors (SBR)s with anaerobic hydraulic retention time (HRT) of 0.8, 2, and 4 h; (ii) batch tests using biomass from a full scale biological nutrient removal (BNR) plant; and (iii) activated sludge modeling (BioWin 4.1 simulation). The results from long-term SBRs operation showed that phosphorus removal was correlated to the ratio of filtered COD (FCOD) to total phosphorus (TP) in the influent. Under conditions with low FCOD/TP ratio (average of 20) in the influent, extending anaerobic HRT to 4 h in the presence of pCOD did not significantly improve overall phosphorous removal. During the period with high FCOD/TP ratio (average of 37) in the influent, all SBRs removed phosphorous completely, and the long anaerobic HRT did not have negative effect on overall phosphorous removal. The batch tests also showed that pCOD at different concentration during 4 h test did not affect the rate of anaerobic phosphorus release. The rate of anaerobic hydrolysis of pCOD was significantly low and extending the anaerobic HRT was ineffective. The simulation (BioWin 4.1) of SBRs with low influent FCOD/TP ratio showed that the default kinetics of anaerobic hydrolysis in ASM2d overestimated phosphorous removal in the SBRs (high anaerobic hydrolysis of pCOD). The default anaerobic hydrolysis rate in BioWin 4.1 (ten times lower) could produce similar phosphorous removal to that in the experiment. Results showed that the current kinetics of anaerobic hydrolysis in ASM2d could lead to considerable error in predicting phosphorus removal in processes with extended anaerobic HRT. Biotechnol. Bioeng. 2016;113: 2377-2385. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

In this paper, an atmospheric pressure dual-frequency (50 kHz/33 MHz) micro-plasma jet was used to deposit organosilicon film. The discharge generated in atmospheric environment. Plasma composition was characterized by optical emission spectroscopy. With introduction of tetraethyl orthosilicate, we observed various spectra, for example Si(251.6 nm), OH(308.9 nm), C(247.8 nm), O(777.5 nm). Abundant reactive radical species which are benefit to film deposition were generated in plasma. The deposited film was characterized by scanning electron microscopy, X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. The film is mostly composed of Si and O. The film has Si-O-Si backbone with a small number of organic component (-CHx). (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Many flooding-tolerant species are clonal plants; however, the effects of physiological integration on plant responses to flooding have received limited attention. We hypothesise that flooding can trigger changes in metabolism of carbohydrates and ROS (reactive oxygen species) in clonal plants, and that physiological integration can ameliorate the adverse effects of stress, subsequently restoring the growth of flooded ramets. In the present study, we conducted a factorial experiment combining flooding to apical ramets and stolon severing (preventing physiological integration) between apical and basal ramets of Cynodon dactylon, which is a stoloniferous perennial grass with considerable flooding tolerance. Flooding-induced responses including decreased root biomass, accumulation of soluble sugar and starch, as well as increased activity of superoxide dismutase ( SOD) and ascorbate peroxidase ( APX) in apical ramets. Physiological integration relieved growth inhibition, carbohydrate accumulation and induction of antioxidant enzyme activity in stressed ramets, as expected, without any observable cost in unstressed ramets. We speculate that relief of flooding stress in clonal plants may rely on oxidising power and electron acceptors transferred between ramets through physiological integration. [ABSTRACT FROM AUTHOR]

We analyzed global patterns of expression in genes related to glutamatergic neurotransmission (glutamatergic genes) in healthy human adult brain before determining the effects of chronic alcohol and cocaine exposure on gene expression in the hippocampus. RNA-Seq data from ' BrainSpan' was obtained across 16 brain regions from nine control adults. We also generated RNA-Seq data from postmortem hippocampus from eight alcoholics, eight cocaine addicts and eight controls. Expression analyses were undertaken of 28 genes encoding glutamate ionotropic ( AMPA, kainate, NMDA) and metabotropic receptor subunits, together with glutamate transporters. The expression of each gene was fairly consistent across the brain with the exception of the cerebellum, the thalamic mediodorsal nucleus and the striatum. GRIN1, encoding the essential NMDA subunit, had the highest expression across all brain regions. Six factors accounted for 84% of the variance in global gene expression. GRIN2B (encoding GluN2B), was up-regulated in both alcoholics and cocaine addicts ( FDR corrected P = 0.008). Alcoholics showed up-regulation of three genes relative to controls and cocaine addicts: GRIA4 (encoding GluA4), GRIK3 ( GluR7) and GRM4 ( mGluR4). Expression of both GRM3 ( mGluR3) and GRIN2D ( GluN2D) was up-regulated in alcoholics and down-regulated in cocaine addicts relative to controls. Glutamatergic genes are moderately to highly expressed throughout the brain. Six factors explain nearly all the variance in global gene expression. At least in the hippocampus, chronic alcohol use largely up-regulates glutamatergic genes. The NMDA GluN2B receptor subunit might be implicated in a common pathway to addiction, possibly in conjunction with the GABAB1 receptor subunit. [ABSTRACT FROM AUTHOR]

We investigated the effects of prophylactic nucleoside analogue treatment on HBV activation in patients with antibodies against core antigen ( HBc Ab+) patients undergoing immunosuppressive therapy. Patients (113), who were HBc Ab+, with various autoimmune diseases, undergoing immunosuppressive therapy, were divided into two groups. The control group, not treated with antivirals, and the prophylactic group, treated with antiviral drugs. The two groups were evaluated for changes in serum biochemical marker (alanine aminotransferase ALT), virological marker ( HBV DNA) and for seroconversion. In the control group, the number of patients with an increase in ALT in patients with isolated HBc Ab and HBc Ab and antibodies against HBs Ag ( HBs Ab +) were five (20.0%) and one (2.8%), respectively ( P < 0.05). There were six cases (24.0%) with an increase in HBV DNA in the isolated HBc Ab+ subgroup and one case (2.8%) in HBs Ab+/ HBc Ab+ subgroup ( P < 0.05). In the HBc Ab+ only population, six patients (24.0%) in the control group had an increase in HBV DNA compared with none in the antiviral prophylactic group ( P < 0.05). One patient (4.0%) with HBc Ab+ in the control group underwent an HBs Ag seroconversion when receiving immunosuppressive therapy for 18 months, while none in the antiviral prophylactic group underwent reversion to HBs Ag positivity ( P = 0.4949). Under immunosuppressive condition, the risk of HBV activation was much higher in patients with HBc Ab than in patients with both HBc Ab and antibodies to HBs Ab group. Antiviral prophylactic therapy could significantly reduce the risk of HBV reactivation. [ABSTRACT FROM AUTHOR]

Background Males have a strikingly increased risk of advanced liver disease. This study was designed to investigate the association between sex hormone levels and different disease states in hepatitis B virus ( HBV)-infected male patients. Methods Two hundred and fifty-two male patients, including 30 with acute hepatitis B ( AHB), 127 with chronic hepatitis B ( CHB) and 95 with chronic severe hepatitis B ( CSHB), and 48 healthy controls ( HCs) were enroled in this study. All patients were followed for 4 months. The primary end point was in-hospital mortality at the end of 90 days. At study entry, a blood sample was collected from all subjects to examine liver function, renal function and sex hormone levels (serum total testosterone and oestradiol). A total of nine clinical chemistry and biochemical variables were analyzed for possible association with outcomes by using Cox proportional hazards and multiple regression models. Results We demonstrated that in CSHB and CHB patients, oestradiol levels were significantly increased compared with HCs and AHB patients, whereas no significant differences were observed in AHB patients and HCs. All male patients had normal levels of testosterone which were not significantly different compared with those of HCs. Increased oestradiol levels were clinically associated with severe liver disease, and increased 3-month mortality rate. Multivariate analysis demonstrated that oestradiol and the model for end-stage liver disease ( MELD) score were independent predictors for mortality (both P < 0.001). Conclusion Oestradiol levels are significantly increased in male patients with hepatitis B, and were associated with the severity of liver disease. Moreover, elevation of oestradiol is an independent predictive factor for the 3-month mortality rate in male patients with hepatitis B. [ABSTRACT FROM AUTHOR]

The fire performance of polyamide 6 (PA6) blended with phenyl phosphonic acid functionalized halloysite nanotubes (PPA-HNTs) is evaluated in order to determine if there is any fire performance gains over the unmodified composite. In the continuing search for safe halogen-free fire retardants for polymers, and the desire to more fully capture the advantages of nano-materials, this research seeks to utilize any synergy which might result in improved fire performance of PA6, via the known advantages offered by nano particles and phosphorus-based compounds. HNTs offer the ability for functionalization by exchange at their hydroxyl sites, while PPA can readily attach at these sites because of its acidity. In this context, the nanotubes act as a carrier for the acid within the polyamide polymeric matrix because it is readily intercalated and functionalized with the acid. The intercalated nano particles are added to the polyamide via melt extrusion and then analyzed using thermal analysis and cone calorimetry. The key finding from this work is that functionalization of HNTs with PPA, followed by blending into PA6 results in a significant improvement in fire performance by altering the combustion dynamics of the polymer. This work proposes a new synergistic fire retardant system for polyamides utilising relatively safe and inexpensive components. More broadly, the concept of using a carrier such as HNTs, which is so easily functionalized, can be applied to other thermoplastic materials, and other additives, for improvements in material properties other than fire. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A reciprocal relationships between osteogenesis and adipogenesis has been observed in vitro and in vivo, and mechanical stretch has been believed to be a regulating factor of osteo-adipogenic axis differentiation of mesenchymal stem cells. In this study, rat adipose stem cells (ASCs) were isolated and cultured in adipogenic or normal medium. Their exposure to cyclic mechanical stretch (2000 με, 1 Hz) in the presence of adipogenic medium decreased mRNA and protein level of PPAR-γ, and increased Runx2 mRNA and protein levels as well as Pref-1 mRNA level, compared to static samples. ASCs cultured in normal medium without adipogenic induction did not show any significant change in mRNA expression of PPAR-γ, Runx2, nor Pref-1 irrespective of mechanical loading. Stretching induced phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) during the induction period. It was concluded that mechanical stretch inhibited adipogenesis and stimulated osteogenesis of these ASCs in the presence of adipogenic medium and that ERK1/2 activation may be involved in the mechanical stress-induced trans-differentiation. [ABSTRACT FROM AUTHOR]

Genetic variability within and among 14 Chinese natural populations of Lespedeza Michx. Used mainly for wildlife food and cover and for erosion control was evaluated on the basis of morphological characteristics, allozyme markers and random amplified polymorphic DNAs (RAPDs). All methods disclosed a high degree of allelic heterogeneity among samples, also revealing a high degree of gene diversity. Genetic variation among populations was higher for RAPD than for enzyme loci. Correlation between morphological, allozyme and RAPD distance matrices were calculated by Mantel’ tests. There was a little disparity between the three level's distances on population relationships. However, there is a weak significant correlation (P < 0.001) between morphology and allozyme distances as well as morphology and RAPD distances, and the test of this correlation is very high. [ABSTRACT FROM AUTHOR]

The article examines the mechanically-induced surface damage introduced during scratching of polyethylene-clay nanocomposites using electron microscopy. The role of clay in reducing the susceptibility to surface deformation is estimated from the characteristics of surface morphology and the scratch deformation parameters. The scratch deformation behavior is explained in terms of tensile modulus, percentage crystallinity, elastic recovery and scratch hardness.

Conventional PCR and two real-time PCR (RTi-PCR) methods were developed and compared using the primer pairs CQULA03F/CQULA03R and CQULA04F/CQULA04R, and TaqMan probe CQULAP1 designed from a species-specific sequence of the rplJ/rplL ribosomal protein gene, for diagnosis of citrus huanglongbing (HLB) disease in southern China. The specificity and sensitivity of the three protocols for detecting ‘ Candidatus Liberibacter asiaticus’ in total DNA extracts of midribs collected from infected citrus leaves with symptoms in Guangxi municipality, Jiangxi Province and Zhejiang Province, were tested. Sensitivities using extracted total DNA (measured as copy number, CN per µL of recombinant plasmid solution) were 439·0 (1·30 × 105 CN µL−1), 4·39 (1·30 × 103 CN µL−1) and 0·44 fg µL−1 (1·30 × 102 CN µL−1) for conventional PCR, TaqMan and SYBR Green I (SGI) RTi-PCR, respectively. SGI RTi-PCR was the most sensitive, but its specificity needed to be confirmed by running a melt-curve assay. The TaqMan RTi-PCR assay was rapid and had the greatest specificity. Concerning the correlation of PCR detection results with the various HLB symptoms, uneven mottling of leaves had the highest positive rate (96·50%), indicating that leaf mottling was the most reliable symptom for field surveys. Dynamic analysis results from the TaqMan assays showed that the titre (CN) g−1 citrus tissue of ‘ Ca. L. asiaticus’ was highest between October and December (threshold cycle ( Ct) average = 29·3, CN = 3·35 × 107) and lowest between March and May ( Ct average = 32·0, CN = 5·10 × 106) in 2004 and 2005. The optimized molecular-based assays should prove useful for presymptom diagnosis of HLB disease, monitoring and identification of ‘ Ca. L. asiaticus’, and field epidemic regulation. [ABSTRACT FROM AUTHOR]

Abstract: Coronavirus envelope (E) protein is a small integral membrane protein with multi-functions in virion assembly, morphogenesis and virus–host interaction. Different coronavirus E proteins share striking similarities in biochemical properties and biological functions, but seem to adopt distinct membrane topology. In this report, we study the membrane topology of the SARS-CoV E protein by immunofluorescent staining of cells differentially permeabilized with detergents and proteinase K protection assay. It was revealed that both the N- and C-termini of the SARS-CoV E protein are exposed to the cytoplasmic side of the membranes (NcytoCcyto). In contrast, parallel experiments showed that the E protein from infectious bronchitis virus (IBV) spanned the membranes once, with the N-terminus exposed luminally and the C-terminus exposed cytoplasmically (Nexo(lum)Ccyto). Intriguingly, a minor proportion of the SARS-CoV E protein was found to be modified by N-linked glycosylation on Asn 66 and inserted into the membranes once with the C-terminus exposed to the luminal side. The presence of two distinct membrane topologies of the SARS-CoV E protein may provide a useful clue to the pathogenesis of SARS-CoV. [Copyright &y& Elsevier]

Studying the association between microbes and diseases not only aids in the prevention and diagnosis of diseases, but also provides crucial theoretical support for new drug development and personalized treatment. Due to the time-consuming and costly nature of laboratory-based biological tests to confirm the relationship between microbes and diseases, there is an urgent need for innovative computational frameworks to anticipate new associations between microbes and diseases. Here, we propose a novel computational approach based on a dual branch graph convolutional network (GCN) module, abbreviated as DBGCNMDA, for identifying microbe-disease associations. First, DBGCNMDA calculates the similarity matrix of diseases and microbes by integrating functional similarity and Gaussian association spectrum kernel (GAPK) similarity. Then, semantic information from different biological networks is extracted by two GCN modules from different perspectives. Finally, the scores of microbe-disease associations are predicted based on the extracted features. The main innovation of this method lies in the use of two types of information for microbe/disease similarity assessment. Additionally, we extend the disease nodes to address the issue of insufficient features due to low data dimensionality. We optimize the connectivity between the homogeneous entities using random walk with restart (RWR), and then use the optimized similarity matrix as the initial feature matrix. In terms of network understanding, we design a dual branch GCN module, namely GlobalGCN and LocalGCN, to fine-tune node representations by introducing side information, including homologous neighbour nodes. We evaluate the accuracy of the DBGCNMDA model using five-fold cross-validation (5-fold-CV) technique. The results show that the area under the receiver operating characteristic curve (AUC) and area under the precision versus recall curve (AUPR) of the DBGCNMDA model in the 5-fold-CV are 0.9559 and 0.9630, respectively. The results from the case studies using published experimental data confirm a significant number of predicted associations, indicating that DBGCNMDA is an effective tool for predicting potential microbe-disease associations., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Liver fibrosis is a persistent damage repair response triggered by various injury factors, which leads to an abnormal accumulation of extracellular matrix within liver tissue samples. The current clinical treatment of liver fibrosis is currently ineffective; therefore, elucidating the mechanism of liver fibrogenesis is of significant importance. Herein, the function and related mechanisms of lncRNA Snhg12 within hepatic fibrosis were investigated. Snhg12 expression was shown to be increased in mouse hepatic fibrotic tissue samples, and Snhg12 knockdown suppressed hepatic pathological injury and down-regulated the expression levels of fibrosis-associated proteins. Mechanistically, Snhg12 played a role in the early activation of mouse hepatic stellate cells (mHSCs) based on bioinformatics analysis, and Snhg12 was positively correlated with Igfbp3 expression. Further experimental results demonstrated that Snhg12 knockdown impeded mHSCs proliferation and activation and also downregulated the protein expression of Igfbp3. Snhg12 could interact with IGFBP3 and boost its protein stability, and overexpression of Igfbp3 partially reversed the inhibition of mHSCsproliferation and activation by the knockdown of Snhg12 . In conclusion, LncRNA Snhg12 mediates liver fibrosis by targeting IGFBP3 and promoting its protein stability, thereby promoting mHSC proliferation and activation. Snhg12 has been identified as an underlying target for treating liver fibrosis., Competing Interests: The authors confirm that there are no conflicts of interest., (© 2024 The Authors. Journal of Cell Communication and Signaling published by John Wiley & Sons Ltd.)

Foodborne illnesses, particularly those caused by Salmonella enterica with its extensive array of over 2600 serovars, present a significant public health challenge. Therefore, prompt and precise identification of S. enterica serovars is essential for clinical relevance, which facilitates the understanding of S. enterica transmission routes and the determination of outbreak sources. Classical serotyping methods via molecular subtyping and genomic markers currently suffer from various limitations, such as labour intensiveness, time consumption, etc. Therefore, there is a pressing need to develop new diagnostic techniques. Surface-enhanced Raman spectroscopy (SERS) is a non-invasive diagnostic technique that can generate Raman spectra, based on which rapid and accurate discrimination of bacterial pathogens could be achieved. To generate SERS spectra, a Raman spectrometer is needed to detect and collect signals, which are divided into two types: the expensive benchtop spectrometer and the inexpensive handheld spectrometer. In this study, we compared the performance of two Raman spectrometers to discriminate four closely associated S. enterica serovars, that is, S. enterica subsp. enterica serovar dublin, enteritidis, typhi and typhimurium. Six machine learning algorithms were applied to analyse these SERS spectra. The support vector machine (SVM) model showed the highest accuracy for both handheld (99.97%) and benchtop (99.38%) Raman spectrometers. This study demonstrated that handheld Raman spectrometers achieved similar prediction accuracy as benchtop spectrometers when combined with machine learning models, providing an effective solution for rapid, accurate and cost-effective identification of closely associated S. enterica serovars., (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Myocardial ischemia/reperfusion (I/R) injury is the primary cause of heart damage in the treatment of myocardial infarction, and the imbalance of the energy metabolism in the pathogenesis of myocardial I/R is one of the main triggers of cardiac dysfunction. Monocarboxylate transporter 4 (MCT4) is a key transporter of lactate, which plays a vital role in cellular metabolism. The present study investigated the role and underlying mechanism of MCT4 in myocardial I/R injury. The results of this study showed that MCT4 was upregulated during oxygen-glucose deprivation (OGD) and restored after reoxygenation in cardiomyocytes HL-1. Interestingly, the overexpression of MCT4 increased cell viability and decreased apoptosis of OGD/R-induced HL-1 cells. Furthermore, MCT4 boosted glucose uptake and lactate levels and promoted protein expression of glycolysis regulator LDHA, while also impeding oxidative phosphorylation (OXPHOS) regulators C-MYC and NDUFB8 in OGD/R-induced HL-1 cells. A reduction in reactive oxygen species and oxidative stress markers malonaldehyde and superoxide dismutase was also observed within the OGD/R stimulated HL-1 cells. Additionally, the in vivo exogenous application of MCT4 restored cardiac function, as demonstrated by the reduced infarct size and decreased myocardial apoptosis in I/R rats. OXPHOS and oxidative stress declined, while glycolysis was activated when the I/R mice were injected with AAV-MCT4. Our findings indicate that MCT4 could exert a cardioprotective effect after myocardial I/R injury by inducing OXPHOS/glycolysis interconversion and inhibiting oxidative stress., (© 2023 John Wiley & Sons Australia, Ltd.)

A digital approach is described for fabricating a splinted framework and custom open tray for the impression of multiple implants based on a virtually created implant cast with the digital prediction of the future impression coping positions. In this technique, impression copings to be used in the definitive impression-making process were digitally scanned and aligned to a preliminary cast using installed protective caps of screw-retained abutments as references, which resulted in a virtual cast that offers information both about the impression coping positions and their surrounding tissues and could allow a splinted framework and custom open tray to be digitally designed and fabricated. Creation of a virtual cast through digital technologies eliminates the traditional manual splinted framework and custom tray fabrication procedures. Additionally, only one set of impression copings and analogs is needed in this technique, thereby reducing treatment time and cost. It also offers a splinted framework and custom open tray with consistent quality., (© 2023 by the American College of Prosthodontists.)

Objective: To date, there is no consensus on the surgery strategies of cranioplasty (CP) and ventriculoperitoneal shunt (VPS) placement. This meta-analysis aimed to investigate the safety of staged and simultaneous operation in patients with comorbid cranial defects with hydrocephalus to inform future surgery protocols., Methods: A meta-analysis of PubMed, Ovid, Web of Science, and Cochrane Library databases from the inception dates to February 8, 2023 adherent to PRISMA guidelines was conducted. The pooled analyses were conducted using RevMan 5.3 software. The outcomes included postoperative infection, reoperation, shunt obstruction, hematoma, and subdural effusion., Results: Of the 956 studies initially retrieved, 10 articles encompassing 515 patients were included. Among the total patients, 193 (37.48%) and 322 (62.52%), respectively, underwent simultaneous and staged surgeries. The finding of pooled analysis indicated that staged surgery was associated with lower rate of subdural effusion (14% in the simultaneous groups vs. 5.4% in the staged groups; OR = 2.39, 95% CI: 1.04-5.49, p = 0.04). However, there were no significant differences in overall infection (OR = 1.92, 95% CI: 0.74-4.97, p = 0.18), central nervous system infection (OR = 1.50, 95% CI: 0.68-3.31, p = 0.31), cranioplasty infection (OR = 1.58, 95% CI: 0.50-5.00, p = 0.44), shunt infection (OR = 1.30, 95% CI: 0.38-4.52, p = 0.67), reoperation (OR = 1.51, 95% CI: 0.38-6.00, p = 0.55), shunt obstruction (OR = 0.73, 95% CI: 0.25-2.16, p = 0.57), epidural hematoma (OR = 2.20, 95% CI: 0.62-7.86, p = 0.22), subdural hematoma (OR = 1.20, 95% CI: 0.10-14.19, p = 0.88), and intracranial hematoma (OR = 1.31, 95% CI: 0.42-4.07, p = 0.64). Moreover, subgroup analysis failed to yield new insights., Conclusions: Staged surgery is associated with a lower rate of postoperative subdural effusion. However, from the evidence of sensitivity analysis, this result is not stable. Therefore, our conclusion should be viewed with caution, and neurosurgeons in practice should make individualized decisions based on each patient's condition and cerebrospinal fluid tap test., (© 2023 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Lipoxin A4 (LXA4) has been identified as the braking signal of inflammation, but the specific role of LXA4 in regulating the regenerative potential of periodontal ligament stem cells (PDLSCs) remains unclear. The aim of this study was to investigate whether and, if so, how LXA4 improves the osteogenic differentiation of PDLSCs in a lipopolysaccharide (LPS)-induced inflammatory environment. We detected the effects of LXA4 on the osteogenic differentiation of PDLSCs in vitro and explored the bone regenerative potential of LXA4-treated inflammatory PDLSCs in vivo using a calvarial critical sized defect model in male rats. RNA sequencing, real-time PCR and western blot were performed to elucidate the relevant potential mechanisms. Results showed that LXA4 promoted the proliferation, migration and osteogenic differentiation of PDLSCs in vitro, and effectively improved the impaired osteogenic capacity of PDLSCs induced by LPS both in vitro and in vivo. Mechanistically, LXA4 significantly promoted the PI3K/AKT phosphorylation under inflammatory conditions. Additionally, LY294002 (a PI3K inhibitor) blocked the effect of LXA4, suggesting that the PI3K/AKT pathway is a key signaling pathway that mediates the effect of LXA4 on the osteogenesis of inflammatory PDLSCs. These findings indicate LXA4 may be a promising strategy for periodontal regeneration using inflammatory PDLSCs., (© 2023 Scandinavian Division of the International Association for Dental Research. Published by John Wiley & Sons Ltd.)

Objectives: Subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are known as the preclinical and early stage of Alzheimer's disease (AD). The dorsal attention network (DAN) is mainly responsible for the "top-down" attention process. However, previous studies mainly focused on single functional modality and limited structure. This study aimed to investigate the multimodal alterations of DAN in SCD and aMCI to assess their diagnostic value in preclinical and early-stage AD., Methods: Resting-state functional magnetic resonance imaging (MRI) was carried out to measure the fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and functional connectivity (FC). Structural MRI was used to calculate the gray matter volume (GMV) and cortical thickness. Moreover, receiver-operating characteristic (ROC) analysis was used to distinguish these alterations in SCD and aMCI., Results: The SCD and aMCI groups showed both decreased ReHo in the right middle temporal gyrus (MTG) and decreased GMV compared to healthy controls (HCs). Especially in the SCD group, there were increased fALFF and increased ReHo in the left inferior occipital gyrus (IOG), decreased fALFF and increased FC in the left inferior parietal lobule (IPL), and reduced cortical thickness in the right inferior temporal gyrus (ITG). Furthermore, functional and structural alterations in the SCD and aMCI groups were closely related to episodic memory (EM), executive function (EF), and information processing speed (IPS). The combination of multiple indicators of DAN had a high accuracy in differentiating clinical stages., Conclusions: Our current study demonstrated functional and structural alterations of DAN in SCD and aMCI, especially in the MTG, IPL, and SPL. Furthermore, cognitive performance was closely related to these significant alterations. Our study further suggested that the combined multiple indicators of DAN could be acted as the latent neuroimaging markers of preclinical and early-stage AD for their high diagnostic value., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: The microbiome associations of food protein-induced enterocolitis syndrome (FPIES) are understudied. We sought to prospectively define the clinical features of FPIES in a birth cohort, and investigate for the evidence of gut dysbiosis., Methods: We identified children diagnosed with FPIES in the Gastrointestinal Microbiome and Allergic Proctocolitis Study, a healthy infant cohort. Children were assessed and stools were collected at each well child visit. The clinical features of the children with FPIES were summarized. Stool microbiome was analyzed using 16S rRNA sequencing comparing children with and without FPIES., Results: Of the 874 children followed up for 3 years, 8 FPIES cases (4 male) were identified, yielding a cumulative incidence of 0.92%. The most common triggers were oat and rice (n = 3, each) followed by milk (n = 2). The children with FPIES were more likely to have family history of food allergy (50% vs. 15.9% among unaffected, p = .03). The average age of disease presentation was 6 months old. During the first 6 months of life, stool from children with FPIES contained significantly less Bifidobacterium adolescentis, but more pathobionts, including Bacteroides spp. (especially Bacteroides fragilis), Holdemania spp., Lachnobacterium spp., and Acinetobacter lwoffii. The short-chain fatty acid (SCFA)-producing Bifidobacterium shunt was expressed significantly less in the stool from FPIES children., Conclusions: In this cohort, the cumulative incidence over the 3-year study period was 0.92%. During the first 6 months of life, children with FPIES had evidence of dysbiosis and SCFA production pathway was expressed less in their stool, which may play an important role in the pathogenesis of FPIES., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

With the widespread application of digital impression techniques in prosthetic dentistry, accurate intraoral scan mounting, and virtual articulator parameters setting as per patients' anatomic structures are essential for treatment planning and restoration fabrication, especially for complex rehabilitation cases; meanwhile, marginal fit checking, occlusal adjustment, and porcelain layering of restorations are also crucial procedures in all cases in which the analog procedure to mount maxillary arches on a mechanical articulator is still required. This technique article presents an indirect digital approach that can first achieve virtual intraoral scan mounting and sagittal condylar inclination value setting of an Artex virtual articulator based on bony structures provided by a single cone beam computed tomography scan. It then facilitates the transfer of virtually mounted intraoral scans from the virtual articulator to the matched Artex mechanical articulator by relating a digitally scanned mounting plate of the Artex mechanical articulator to the virtual articulator, printing the intraoral scan and mounting plate scan assembly, and then mounting the printed casts on the mechanical articulator based on the printed mounting plate. This technique eliminates the conventional facebow transfer and protrusive bite registration procedures and offers a straightforward approach for the seamless integration of virtual environments and analog workflows into clinical practice. It aids in the design of restorations that are harmonious with the mandibular movements and reduces chairside adjustment time., (© 2022 by the American College of Prosthodontists.)

Customized cast orientations and parameter settings of the virtual articulator according to the patient's condyles are indispensable parts of today's digital workflows in prosthodontics. This article describes a digital technique to align the intraoral scans to a virtual articulator by using a facial scanner to locate the patient's cutaneous landmarks of the arbitrary hinge axis and the reference plane, and to customize the sagittal condylar inclination of the virtual articulator through a digital protrusive interocclusal record and a dental computer-aided design software program. It enables individual cast orientations and virtual articulator parameter settings without conventional facebow transferring and bite registration procedures and can be easily integrated with most virtual articulator systems on the market to allow clinicians and technicians to work in a complete digital workflow and facilitate customized treatment planning and dental prosthesis fabrication., (© 2021 by the American College of Prosthodontists.)

Background Whether intravenous thrombolysis before mechanical thrombectomy provides additional benefit for functional outcome in acute ischemic stroke remains uncertain. We performed a meta-analysis to compare the outcomes of direct mechanical thrombectomy (dMT) to mechanical thrombectomy with bridging using intravenous thrombolysis (bridging therapy [BT]) in patients with acute ischemic stroke. Methods and Results We performed a literature search in the PubMed, Excerpta Medica database, and Cochrane Central Register of Controlled Trials from January 1, 2003, to April 26, 2021. We included randomized clinical trials and observational studies that reported the 90-day functional outcome in patients with acute ischemic stroke undergoing dMT compared with BT. The 12 included studies (3 randomized controlled trials and 9 observational studies) yielded 3924 participants (mean age, 68.0 years [SD, 13.1 years]; women, 44.2%; 1887 participants who received dMT and 2037 participants who received BT). A meta-analysis of randomized controlled trial and observational data revealed similar 90-day functional independence (odds ratio [OR], 1.04; 95% CI, 0.90-1.19), mortality (OR, 1.03; 95% CI, 0.78-1.36), and successful recanalization (OR, 0.93; 95% CI, 0.76-1.14) for patients treated with dMT or BT. Compared with those in the BT group, patients in the dMT group were less likely to experience symptomatic intracranial hemorrhage (OR, 0.68; 95% CI, 0.51-0.91; P =0.008) or any intracranial hemorrhage (OR, 0.71; 95% CI, 0.61-0.84; P <0.001). Conclusions In this meta-analysis of patients with acute ischemic stroke, we found no significant differences in 90-day functional outcome or mortality between dMT and BT, but a lower rate of symptomatic intracranial hemorrhage for dMT. These findings support the use of dMT without intravenous thrombolysis bridging therapy. Registration URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: 42021234664.

Tumour M2-pyruvate kinase (TUM2-PK) is up-regulated in many human cancers. This study was to evaluate the clinical value of serum TUM2-PK in early-stage non-small cell lung cancer (NSCLC) patients. A total of 162 consecutive early-stage NSCLC patients were enrolled and followed up after tumour resection. Serum TUM2-PK level was detected by enzyme-linked immunosorbent assay (ELISA) in NSCLC patients, 50 benign pulmonary disease patients and 102 healthy controls. The TUM2-PK level in NSCLC patients was higher than that of healthy controls (P < .001) and benign pulmonary disease patients (P < .001). A threshold of 30 U/mL could be used to diagnose early-stage NSCLC with 71.6% sensitivity and 98.0% specificity. The 5-year overall survival rate in patients with high TUM2-PK level was lower than that of patients with low TUM2-PK level (P = .009). Multivariable Cox regression showed that high TUM2-PK level was an independent risk factor for overall survival (HR = 2.595, 95% CI: 1.231-5.474, P = .012). High serum TUM2-PK level could be a potential biomarker for diagnosis and prognosis of early-stage NSCLC patients., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Mitochondria are central eukaryotic organelles in cellular metabolism and ATP production. Mitochondrial DNA (mtDNA) alterations have been implicated in the development of colorectal cancer (CRC). However, there are few reports on the association between mtDNA haplogroups or single nucleotide polymorphisms (SNPs) and the risk of CRC. The mtDNA of 286 Northern Han Chinese CRC patients were sequenced by next-generation sequencing technology. MtDNA data from 811 Han Chinese population controls were collected from two public data sets. Then, logistic regression analysis was used to determine the effect of mtDNA haplogroup or SNP on the risk of CRC. We found that patients with haplogroup M7 exhibited a reduced risk of CRC when compared to patients with other haplogroups (odds ratio [OR] = 0.532, 95% confidence interval [CI] = 0.285-0.937, p = 0.036) or haplogroup B (OR = 0.477, 95% CI = 0.238-0.916, p = 0.030). Furthermore, haplogroup M7 was still associated with the risk of CRC when the validation and combined control cohort were used. In addition, several haplogroup M7 specific SNPs, including 199T>C, 4071C>T and 6455C>T, were significantly associated with the risk of CRC. Our results indicate the risk potential of mtDNA haplogroup M7 and SNPs in CRC in Northern China., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Methanol is a promising feedstock for biomanufacturing of fuels and chemicals. Although efforts have been made to engineer platform microorganisms for methanol bioconversion, the substrate uptake and cell growth rates on methanol are still unsatisfactory, suggesting certain limiting factors remain unsolved. Herein, we analysed the global metabolic regulation changes between an evolved methanol-dependent Corynebacterium glutamicum mutant and its ancestral strain by transcriptome analysis. Many genes involved in central metabolism including glycolysis, amino acid biosynthesis and energy generation were regulated, implying the adaptive laboratory evolution reprogrammed the cellular metabolism for methanol utilization. We then demonstrated that nitrate could serve as a complementary electron acceptor for aerobic methanol metabolism, and the biosynthesis of several amino acids limited methylotrophic growth. Finally, the sedoheptulose bisphosphatase pathway for generating methanol assimilation acceptor was found effective in C. glutamicum. This study identifies limiting factors of methanol metabolism and provides engineering targets for developing superior synthetic methylotrophs., (© 2021 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.)

Increased adenosine helps limit infarct size in ischaemia/reperfusion-injured hearts. In cardiomyocytes, 90% of adenosine is catalysed by adenosine kinase (ADK) and ADK inhibition leads to higher concentrations of both intracellular adenosine and extracellular adenosine. However, the role of ADK inhibition in myocardial ischaemia/reperfusion (I/R) injury remains less obvious. We explored the role of ADK inhibition in myocardial I/R injury using mouse left anterior ligation model. To inhibit ADK, the inhibitor ABT-702 was intraperitoneally injected or AAV9 (adeno-associated virus)-ADK-shRNA was introduced via tail vein injection. H9c2 cells were exposed to hypoxia/reoxygenation (H/R) to elucidate the underlying mechanisms. ADK was transiently increased after myocardial I/R injury. Pharmacological or genetic ADK inhibition reduced infarct size, improved cardiac function and prevented cell apoptosis and necroptosis in I/R-injured mouse hearts. In vitro, ADK inhibition also prevented cell apoptosis and cell necroptosis in H/R-treated H9c2 cells. Cleaved caspase-9, cleaved caspase-8, cleaved caspase-3, MLKL and the phosphorylation of MLKL and CaMKII were decreased by ADK inhibition in reperfusion-injured cardiomyocytes. X-linked inhibitor of apoptosis protein (XIAP), which is phosphorylated and stabilized via the adenosine receptors A2B and A1/Akt pathways, should play a central role in the effects of ADK inhibition on cell apoptosis and necroptosis. These data suggest that ADK plays an important role in myocardial I/R injury by regulating cell apoptosis and necroptosis., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Since SARS-CoV-2 infection was first identified in December 2019, the novel coronavirus-induced pneumonia COVID-19 spread rapidly and triggered a global pandemic. Recent bioinformatics evidence suggested that angiotensin-converting enzyme 2-the main cell entry target of SARS-CoV-2-was predominantly enriched in spermatogonia, Leydig and Sertoli cells, which suggests the potential vulnerability of the male reproductive system to SARS-CoV-2 infection., Objectives: To identify SARS-CoV-2 RNA in seminal plasma and to determine semen characteristics from male patients in the acute and recovery phases of infection., Methods: From February 26 to April 2, 2020, 23 male patients with COVID-19 were recruited. The clinical characteristics, laboratory findings and chest computed tomography scans of all patients were recorded in detail. We also investigated semen characteristics and the viral RNA load in semen from these patients in the acute and recovery phases of SARS-CoV-2 infection using approved methods., Results: The age range of the 23 patients was 20-62 years. All patients tested negative for SARS-CoV-2 RNA in semen specimens. Among them, the virus had been cleared in 11 patients, as they tested negative. The remaining 12 patients tested negative for SARS-CoV-2 RNA in semen samples, but were positive in sputum and fecal specimens. The median interval from diagnosis to providing semen samples was 32 days, when total sperm counts, total motile sperm counts, and sperm morphology of the patients were within normal ranges., Discussion and Conclusion: In this cohort of patients with a recent infection or recovering from COVID-19, there was no SARS-CoV-2 RNA detected in semen samples, which indicates the unlikely possibility of sexual transmission through semen at about 1 month after first detection., (© 2020 American Society of Andrology and European Academy of Andrology.)

Taurine upregulated gene 1 (Tug1) is a novel lncRNA that participates in growth, and the abnormal expression of Tug1 related to mouse islet cell dysfunction. A recent study revealed that intrauterine growth retardation (IUGR) related to the pathogenesis of diabetes. Here, we aimed to explore the role and mechanism of Tug1 in IUGR-mediated islet dysfunction. We observed that newborn IUGR mice had lower body and pancreas weight and smaller islets than newborn control mice. After IUGR mice were given a normal diet, they showed catch-up growth and abnormal glucose tolerance; however, the pancreas/body weight ratio remained low. Blood glucose, serum insulin and related gene expression showed mild recovery after overexpression of Tug1 in IUGR mice. Furthermore, Tug1 was enriched in the nuclei of MIN6 cells. Using RIP and CHIP analyses we found that Tug1 could regulate Hes1 expression by binding to EZH2 to affect insulin synthesis in MIN6 cells. These findings indicate that lncRNA Tug1 could regulate the expression of Hes1 via EZH2-driven H3K27 methylation and affect insulin production. SIGNIFICANCE OF THE STUDY: This study suggests Tug1 as a novel biomarker, as it was shown to regulate β cell function and is worthy of further investigation due to its potential for diabetes treatment., (© 2020 John Wiley & Sons Ltd.)

Dental stem cell-based tooth regeneration is the futuristic treatment for missing teeth. Growth differentiation factor 11 (GDF11), a novel member of the TGF-beta superfamily, has been reported to play a critical role in regulating stem cell differentiation. However, the role of endogenous GDF11 during dental stem cell differentiation remains unknown. Here, we have shown that GDF11 was highly expressed in dental pulp tissues in both mouse and human. Knockdown of endogenous GDF11 in human dental pulp stem cells (hDPSCs) led to comparable proliferation and migration but attenuated odontogenic differentiation as evidenced by alkaline phosphatase and Alizarin Red S staining. In addition, transcriptional levels of odontogenic-related genes were significantly down-regulated according to real-time polymerase chain reaction. Mechanistically, we performed RNA sequencing analysis and found that silencing of endogenous GDF11 compromised the process of ossification and osteoblast differentiation, especially down-regulated transcription expression of Wnt pathway-specific genes. Immunofluorescence staining also showed diminished β-catenin expression and nuclei accumulation after knockdown of endogenous GDF11 in hDPSCs. In summary, our results suggested that endogenous GDF11 positively regulate odontogenic differentiation of hDPSCs through canonical Wnt/β-catenin signalling pathway., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Cripto-1 (CR-1) is related to the biological behaviour and prognosis of carcinomas. The purpose of this study was to investigate the significance of CR-1 expression in surgically resected stage I non-small cell lung cancer (NSCLC). One hundred and forty-eight patients with completely resected stage I NSCLC and available clinical follow-up data were assessed. The protein expression of CR-1 in the tumours was detected by immunohistochemistry. CR-1 was highly expressed in 64 of 148 tumours. Among patients with high CR-1 expression, progression-free survival and overall survival rate were significantly lower than those of patients with low CR-1 levels (P = .013 and P = .019, respectively). The incidence of distant metastasis in patients with high CR-1 expression was significantly higher than that of in patients with low CR-1 expression (57.13% vs 21.43%, P = .001). The results of the multivariate analysis confirmed that a high CR-1 was a significant factor for poor prognosis. In conclusion, CR-1 could be a useful prognostic factor in patients with stage I NSCLC, likely as an indicator of the metastatic propensity of the tumour., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. in both PDF and HTML.)

Ubiquitin-specific protease 34 (USP34), a member of the ubiquitin-specific protease family, regulates osteogenic differentiation of bone marrow mesenchymal stem cells via bone morphogenetic protein signaling. This study aimed to investigate the role of USP34 in fixation of titanium implants in mouse models. Eight-week-old Usp34-knockout (Prx1-Cre;Usp34 f/f ) mice and their Usp34 wild-type (Usp34 f/f ) control littermates were used. Experimental titanium implants were inserted into the distal ends of femurs and the edentulous area of maxillae. Two and four weeks after surgery, samples of femur and maxilla were obtained, and micro-computed tomography scanning, histomorphometric analyses, and push-in tests were performed on the samples. Compared with controls, Prx1-Cre;Usp34 f/f mice showed reduced bone volume for both femurs and maxillae; a decreased femoral bone-implant contact ratio (BIC) at 2 wk [mean (standard error of the mean): 62.17% (2.15%) vs. 44.06% (3.45%)] and 4 wk [72.46% (1.61%) vs. 64.53% (1.93%)]; decreases in femoral bone volume fraction (BV/TV) and push-in resistance; and lower BIC and BV/TV of the maxillae. Taken together, our data demonstrate that specific deletion of Usp34 in mesenchymal stem cells impairs fixation of titanium implants in mice., (© 2020 Eur J Oral Sci.)

Natural products were extracted from traditional Chinese herbal emerging as potential therapeutic drugs for treating cardiovascular diseases. This study examines the role and underlying mechanism of dihydromyricetin (DMY), a natural compound extracted from Ampelopsis grossedentata, in atherosclerosis. DMY treatment significantly inhibits atherosclerotic lesion formation, proinflammatory gene expression and the influx of lesional macrophages and CD4-positive T cells in the vessel wall and hepatic inflammation, whereas increases nitric oxide (NO) production and improves lipid metabolism in apolipoprotein E-deficient (Apoe - / - ) mice. Yet, those protective effects are abrogated by using NOS inhibitor L-NAME in Apoe - / - mice received DMY. Mechanistically, DMY decreases microRNA-21 (miR-21) and increases its target gene dimethylarginine dimethylaminohydrolase-1 (DDAH1) expression, an effect that reduces asymmetric aimethlarginine (ADMA) levels, and increases endothelial NO synthase (eNOS) phosphorylation and NO production in cultured HUVECs, vascular endothelium of atherosclerotic lesions and liver. In contrast, systemic delivery of miR-21 in Apoe - / - mice or miR-21 overexpression in cultured HUVECs abrogates those DMY-mediated protective effects. These data demonstrate that endothelial miR-21-inhibited DDAH1-ADMA-eNOS-NO pathway promotes the pathogenesis of atherosclerosis which can be rescued by DMY. Thus, DMY may represent a potential therapeutic adjuvant in atherosclerosis management., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

In this report, the desymmetrization of cyclic enones under relay Heck conditions with an array of aryl boronic acids, alkenyl triflates and indole derivatives is described. This method grants facile access to diverse γ-functionalized cyclopentenones and δ-functionalized cycloheptenones. Using this approach, a formal synthesis of ( S )-baclofen was completed in high yield and excellent enantioselectivity.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of leading causes of global deaths. This study aimed to explore the role of miR-18a in RAW264.7 cells response to Mtb infection. Exosomes derived from Mtb-infected cells were isolated and further validated by size, transmission electron microscopy and Western blot. RT-PCR was utilized to measure miR-18a expression. Cell viability and ultrastructure were examined by CFU counting, CCK-8 and electron microscope, respectively. Potential target genes of miR-18a were predicted with bioinformatics and further confirmed using RT-PCR, Western blot and laser confocal microscope analysis, respectively. LC3, AMPK and mTOR were measured using Western blot. We found that miR-18a was induced both in Mtb-infected RAW264.7 cells and its derived exosomes compared with the controls. In addition, up-regulation of miR-18a promoted intracellular Mtb survival, attenuated cell viability and reduced LC3-II level, while its down-regulation had the opposite effect. miR-18a overexpression suppressed level of ATM, one possible target of miR-18a, while its underexpression enhanced ATM. We also found that inhibition of ATM induced LC3-II decrease in Mtb-infected cells and could reverse the increase of LC3-II caused by inhibition of miR-18a. Moreover, down-regulation of miR-18a increased p-AMPK level while reduction of ATM could reverse the change. Taken together, our results suggest that miR-18a is up-regulated in macrophages response to Mtb infection, and it promotes intracellular Mtb survival through repressing autophagic process by down-regulation of ATM pathway. This provides new thought for TB pathogenesis, diagnosis and treatment., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Myocardial ischaemia/reperfusion (I/R) injury attenuates the beneficial effects of reperfusion therapy. Poly(ADP-ribose) polymerase (PARP) is overactivated during myocardial I/R injury. Mitophagy plays a critical role in the development of myocardial I/R injury. However, the effect of PARP activation on mitophagy in cardiomyocytes is unknown. In this study, we found that I/R induced PARP activation and mitophagy in mouse hearts. Poly(ADP-ribose) polymerase inhibition reduced the infarct size and suppressed mitophagy after myocardial I/R injury. In vitro, hypoxia/reoxygenation (H/R) activated PARP, promoted mitophagy and induced cell apoptosis in cardiomyocytes. Poly(ADP-ribose) polymerase inhibition suppressed H/R-induced mitophagy and cell apoptosis. Parkin knockdown with lentivirus vectors inhibited mitophagy and prevented cell apoptosis in H/R-treated cells. Poly(ADP-ribose) polymerase inhibition prevented the loss of the mitochondrial membrane potential (ΔΨm). Cyclosporin A maintained ΔΨm and suppressed mitophagy but FCCP reduced the effect of PARP inhibition on ΔΨm and promoted mitophagy, indicating the critical role of ΔΨm in H/R-induced mitophagy. Furthermore, reactive oxygen species (ROS) and poly(ADP-ribosylation) of CypD and TSPO might contribute to the regulation of ΔΨm by PARP. Our findings thus suggest that PARP inhibition protects against I/R-induced cell apoptosis by suppressing excessive mitophagy via the ΔΨm/Parkin pathway., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Thymic stromal lymphopoietin is a key initiator for inducing Th2-type inflammation and a potential therapeutic target for allergic disease. In the present study, the naive human antibody library was enriched using human thymic stromal lymphopoietin (hTSLP) as an antigen by phage display. Single clones were randomly picked from the enriched antibody library after three rounds of selection, and these were expressed for enzyme-linked immunosorbent assay (ELISA). The positive single-chain fragment variables (scFvs) determined by ELISA were further identified by Western blot, Biacore, and flow cytometry. After three rounds of phage display, 35% of the scFv clones were positive by ELISA and could bind well with hTSLP. Further identification revealed that scFv29 had satisfactory characteristics. The scFv29 was specific to hTSLP, and had no cross-reaction with hIL-33, hIL-4, and hIL-13. The scFv29 could bind to hTSLP in competition with the TSLP receptor and could also bind to mouse TSLP. Cellular experiments revealed that mTSLP could stimulate myeloid dendritic cell (DC) to mature, and scFv29 blocking could reduce the maturation rate of DC. These findings suggest that scFv29 could be used as a neutralizing antibody to block the signaling of TSLP, and this work provides the foundation for further study of the therapeutic roles of TSLP in allergic inflammation diseases., (© 2019 International Union of Biochemistry and Molecular Biology, Inc.)