Search

Highlights • Facial nerve lesions could induce plastic changes in sensorimotor cortex. • Distances between blinking and smiling representation sites (B-S-distance) were shorter in patients than in controls. • B-S-distance on affected sides was shorter than unaffected sides in patients. Abstract This study aimed to investigate the cortical functional alterations in patients with unilateral facial synkinesis using the task-designed functional magnetic resonance imaging. Fourteen unilateral synkinesis followed by peripheral facial nerve palsy patients and eighteen healthy adults were recruited in this study. Four facial motor tasks, i.e. left/right blinking and left/right smiling, were performed by each subject during the scans. Based on the activation maps, the spatial distance between the representation sites in the contralateral pre-/post-central gyrus of left or right blinking and smiling tasks (i.e. left/right B-S-distance) were calculated. Patients with unilateral facial synkinesis showed decreased B-S-distances during blinking and smiling tasks on the affected half face (9.68 ± 3.92 mm) compared to both average distances in healthy controls (14.95 ± 5.55 mm; p = 0.002) and unaffected half face tasks in patients (16.19 ± 7.87 mm; p = 0.011). These findings demonstrated cortical reorganization in facial synkinesis and suggested a conceivable mechanism corresponding to the simultaneous facial movement. This potentially provides a new modulation target for preventive, therapeutic and rehabilitative maneuver of this disease. [ABSTRACT FROM AUTHOR]

Background/Aims: This study aims to examine the effect of long noncoding RNA HOST2 (LncRNA HOST2) on epithelial-mesenchymal transition (EMT), proliferation, invasion and migration of hepatocellular carcinoma (HCC) cells via activation of the JAK2-STAT3 signaling pathway. Methods: HCC and para-cancerous tissues were collected from 136 HCC patients. Immunohistochemistry was used to detect the expression of JAK2 and STAT3. HCC SMMC7721 cells were grouped into blank, negative control (NC), HOST2 mimic and HOST2 inhibitor groups. The mRNA and protein expression levels of HOST2, JAK2, STAT3, E-cadherin, vimentin, Snail, Slug, Twist and Zeb1 in tissues and cells were determined by reverse transcription -quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. An MTT assay, scratch test and Transwell assay were applied to measure cell proliferation, migration and invasion, respectively. Results: The levels of JAK2, STAT3 and vimentin were higher in HCC tissues, while the expression of E-cadherin was lower in HCC tissues compared with para-cancerous tissues. The silencing of HOST2 significantly decreased cell proliferation, migration and invasion, reduced the levels of HOST2, JAK2, STAT3 and vimentin, and elevated the expression of E-cadherin. HOST2 silencing also decreased the levels of Snail, Slug and Twist but increased the level of Zeb1 protein, while the opposite findings were observed in the HOST2 mimic group. Conclusion: These results reveal a possible mechanism in HCC in which LncRNA HOST2 may increase EMT and enhance proliferation, invasion and metastasis of HCC cells via activation of the JAK2-STAT3 signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract Background Prospective randomized trials have not been used to evaluate the efficacy of adjuvant therapies after intrahepatic cholangiocarcinoma (ICC) resection. Methods We analyzed data from the Taiwan Cancer Registry database of ICC patients receiving resection. To compare outcomes, patients with ICC were enrolled and categorized into the following adjuvant treatment modality groups: group 1, concurrent chemoradiotherapy (CCRT); group 2, sequential chemotherapy (CT) and radiotherapy (RT); and group 3, CT alone. Results We enrolled 599 patients with resectable ICC who received surgery without distant metastasis. Of these patients, 174 received adjuvant CCRT (group 1), 146 received adjuvant sequential CT and RT (group 2), and 279 received adjuvant CT alone (group 3). Multivariate Cox regression analysis indicated that pathologic stage and positive margin were significantly poor independent predictors. After adjustment for confounders, adjusted hazard ratios (95% confidence intervals) for overall mortality at advanced pathologic stages III and IV were 0.55 (0.41–0.74) and 0.92 (0.70–1.33) in groups 1 and 2, respectively, compared with group 3. Conclusions Adjuvant CCRT improved survival in resected ICC with advanced pathologic stages or a positive margin in early pathologic stages compared with adjuvant CT alone or adjuvant sequential CT and RT. [ABSTRACT FROM AUTHOR]

A series of novel bis‐benzothiazole derivatives with head‐to‐head orientation were designed, synthesized, and evaluated for their anti‐proliferative activities on U937, HL60, and HeLa cells. A significant part of the targets exhibited considerable in vitro anticancer activity, and some of them were more potent than the reference 5‐FU. Molecular modeling, fluorescence, and viscosimetry studies revealed that these compounds could bind into the minor groove of DNA. Amongst them, the most active compound 7 with IC50 in a range of 6.76 to 8.67 μM against the tested three cell lines, which was 1.46–2.47 and 3.48–4.93 times more potent than 5‐FU and Hoechst 33258, respectively, warrant further investigations. [ABSTRACT FROM AUTHOR]

[Display omitted] • A facile photochemical synthetic strategy to support noble metal single atoms onto CeO 2 is developed. • An efficient dechlorination strategy, where the stubborn Cl ions strongly binding to Pt sites are deeply removed from the catalyst, is proposed via photo-deposition. • Surface oxygen on CeO 2 is activated after dechlorination, resulting in enhanced capability of H 2 O dissociation. • The water–gas shift activity is thus promoted. Such strategy shows universality toward different metals, supports and reactions. During regular synthesis, the supported catalysts may suffer from incomplete exposure of metal sites, whose activity may accordingly be limited by the stubborn residues and inert coordination environment. Here we report a photochemical strategy to fabricate promoted Pt-CeO 2 catalysts, where UV-induced deep dechlorination and the following surface oxygen activation are achieved. With a photo-deposition method, the usually neglected stubborn Cl residues are easily removed from Pt-CeO 2. The adjacent oxygen species are activated under UV illumination, whose flexible elimination creates sufficient surface vacancies, resulting in enhanced H 2 O dissociation. The derived catalyst shows excellent performances for the water–gas shift (WGS) reaction. Such strategy shows universality toward different metals, supports and reactions. This work sheds light on the synthesis of robust catalysts, by applying photochemical method for Cl removal and surface oxygen activation. The universal strategy shows great potentials in developing promoted solid catalysts for various heterogeneous reactions. [ABSTRACT FROM AUTHOR]

The white wax secreted by the male insects of the Chinese white wax scale (CWWS) is a natural high-molecular-weight compound with important economic value. However, its regulatory mechanism of wax biosynthesis is still unclear. In this study, a weighted gene coexpression network analysis (WGCNA) was used to analyze transcriptome data of first- and second-instar females, early and late female adults, and first- and second-instar males. A total of 19 partitioned modules with different topological overlaps were obtained, and three modules were identified as highly significant for wax secretion (p < 0.05). A total of 30 hub genes were obtained through screening, among which elongation of very-long-chain fatty acids protein (ELOVL) and fatty acyl-CoA reductase (FAR) are important catalytic enzymes of fatty acid metabolism. Furthermore, their metabolic catalytic products are involved in the synthesis of wax biosynthesis. The results demonstrate that WGCNA can be used for insect transcriptome analysis and effectively screen out the key genes related to wax biosynthesis. [ABSTRACT FROM AUTHOR]

The global healthcare challenge posed by COVID-19 necessitates the continuous exploration for novel antiviral agents. Fucoidans have demonstrated antiviral activity. However, the underlying structure-activity mechanism responsible for the inhibitory activity of fucoidans from Ascophyllum nodosum (FUCA) and Undaria pinnatifida (FUCU) against SARS-CoV-2 remains unclear. FUCA was characterized as a homopolymer with a backbone structure of repeating (1 → 3) and (1 → 4) linked α-l-fucopyranose residues, whereas FUCU was a heteropolysaccharide composed of Fuc1–3Gal1–6 repeats. Furthermore, FUCA demonstrated significantly higher anti-SARS-CoV-2 activity than FUCU (EC50: 48.66 vs 69.52 μg/mL), suggesting the degree of branching rather than sulfate content affected the antiviral activity. Additionally, FUCA exhibited a dose-dependent inhibitory effect on ACE2, surpassing the inhibitory activity of FUCU. In vitro , both FUCA and FUCU treatments downregulated the expression of pro-inflammatory cytokines (IL-6, IFN-α, IFN-γ, and TNF-α) and anti-inflammatory cytokines (IL-10 and IFN-β) induced by viral infection. In hamsters, FUCA demonstrated greater effectiveness in attenuating lung and gastrointestinal injury and reducing ACE2 expression, compared to FUCU. Analysis of the 16S rRNA gene sequencing revealed that only FUCU partially alleviated the gut microbiota dysbiosis caused by SARS-CoV-2. Consequently, our study provides a scientific basis for considering fucoidans as poteintial prophylactic food components against SARS-CoV-2. [Display omitted] • The inhibitory activity of FUCA against SARS-CoV-2 was higher than that of FUCU, possibly due to the branching structure of fucoidan. • FUCA exhibited superior efficacy compared to FUCU in mitigating lung and gastrointestinal tract injuries in SARS-CoV-2-infected hamsters, which was achieved through the inhibition of ACE2 expression and subsequent inflammatory responses. [ABSTRACT FROM AUTHOR]

Aims: Variation in tree litter inputs and understory vegetation caused by human disturbances and climate change in forest plantations can extend to alter forest stability and productivity over time. Here, we explore how tree litter inputs interact with understory plant management to influence belowground processes in a managed forest plantation. Methods: We conducted a two-factor nested experimental manipulation of pine litter and understory vegetation in a nutrient-poor Pinus sylvestris var. mongolica plantation. Three levels of tree litter manipulation (ambient litter, litter removal and litter addition) were nested in two levels of understory manipulation (understory intact and understory removal). After two years of manipulation, mineral soils were analyzed for total and extractable C, N and P concentrations, N mineralization, enzyme activities, as well as the microbial community structure (as indicated by phospholipid fatty acids). Results: Litter removal had little impact on C and nutrient cycling as well as microbial biomass and community structure in this low nutrient pine plantation; however, litter addition and the removal of the understory vegetation had large impacts on these processes. Litter addition elevated soil microbial biomass, acid phosphatase and β-1, 4-glucosidase activities, by a much greater degree when the understory vegetation was intact than when the understory was removed. Litter addition also reduced soil available P by 39% when the understory vegetation was intact, and reduced soil available P by 74% and NO -N by 45% when the understory was removed. Litter addition significantly reduced the ratio of Gram-positive to Gram-negative bacteria as well as the ratio between PLFA markers cy17:0 and 16:1ω7. Understory removal reduced the ratio of PLFA markers cy17:0 to 16:1ω7. Conclusions: Our study results show that, in this managed pine plantation, soil microbial community structure and function were more sensitive to an increase rather than to a decrease in pine litter inputs. Further, we found that the presence of understory vegetation can increase soil microbial biomass and alleviate the reduction in available N and P concentrations induced by pine litter addition. Thus, preservation of the understory vegetation is an effective way to maintain the functional stability of managed forests on nutrient-poor soils. [ABSTRACT FROM AUTHOR]

Background: Salvia Miltiorrhiza Depside Salt for Infusion (SMDS) is made of a group of highly purified listed drugs. However, its safety data is still reported limitedly. Compared with the clinical trials, its safety in the real world setting is barely assessed. Objective: To investigate the safety issues, including adverse events (AEs), adverse events related to SMDS (ADEs), and adverse drug reactions (ADRs) of the SMDS in the real world clinical practice. Methods: This is a prospective, multicenter, pharmacist-led, cohort study in the real world setting. Consecutive patients prescribed with SMDS were all included in 36 sites. Pharmacists were well trained to standardized collect the patients information, including demographics, medical history, prescribing patterns of SMDS, combined medications, adverse events, laboratory investigations, outcomes of the treatment when discharge, and interventions by pharmacists. Adverse events and adverse drug reactions were collected in details. Multivariate possion regression analysis was applied to identify risk factors associated with ADEs using the significance level (α) 0.05. ClinicalTrials.gov Identifier: NCT01872520. Results: Thirty six hospitals were participated in the study and 30180 consecutive inpatients were included. The median age was 62 (interquartile range [IQR], 50–73) years, and male was 17384 (57.60%) among the 30180 patients. The incidences of the AEs, ADEs and ADRs were 6.40%, 1.57% and 0.79%, respectively. There were 9 kinds of new ADEs which were not on the approved label found in the present study. According to the multivariate analysis, male (RR = 1.381, P = 0.009, 95%CI [1.085~1.759]), more concomitant medications (RR = 1.049, P<0.001, 95%CI [1.041~1.057]), longer duration of SMDS therapy (RR = 1.027, P<0.001, 95%CI [1.013~1.041]), higher drug concentration (RR = 1.003, P = 0.014, 95%CI [1.001~1.006]), and resolvent unapproved (RR = 1.900, P = 0.002, 95%CI [1.260~2.866]) were the independent risk factors of the ADEs. Moreover, following the approved indication (RR = 0.655, P<0.001, 95%CI [0.532~0.807]) was associated with lower incidence of ADEs. Conclusions: SMDS was well tolerated in the general population. The incidences of the AEs, ADEs and ADRs were 6.40%, 1.57% and 0.79%, respectively. Several risk factors of its ADEs have been identified. It is recommended to follow the instructions when prescribing and administrating SMDS in the real world clinical practice. [ABSTRACT FROM AUTHOR]

Importance map plays a crucial role in the seam-carving process, a well known image retargeting method. Usually a saliency map (with central bias or single Gaussian priority) is chosen as the importance map. However, we find that direct use of saliency map for seam-carving may cause some unsatisfactory visual effects such as trivial solution or distortion. In this paper, we analyze the reasons and give improved importance map by fusing a multi-Gaussian saliency map (MG-SM) and a revised slant edge saliency map (SE-SM). Specifically for the multi-Gaussian saliency map, we assume that the priori saliency distribution of an image is multi-Gaussian centered at some object centers rather than single Gaussian. Super pixels and sparse representation are used to measure the saliency. For the revised slant edge saliency map, we use wavelet transform to find the slant edges and design to carve seams on the slant edges uniformly. The present method has been extensively tested and more satisfactory experimental results, especially for the slant edge distortion, are obtained than the other methods compared. [ABSTRACT FROM AUTHOR]

Objective: We aimed to characterise glioblastomas of adolescents and young adults (AYAs) that were isocitrate dehydrogenase (IDH) wild type (wt) and H3wt. Materials and Methods: Fifty such patients (aged 16–32) were studied by methylation profiling, targeted sequencing and targeted RNA‐seq. Results: Tumours predominantly clustered into three methylation classes according to the terminology of Capper et al. (2018): (anaplastic) pleomorphic xanthoastrocytoma (PXA) (21 cases), GBM_midline (15 cases) and glioblastoma RTK/mesenchymal (seven cases). Two cases clustered with ANA_PA, four cases with LGG classes and one with GBM_MYCN. Only fifteen cases reached a calibrated score >0.84 when the cases were uploaded to DKFZ Classifier. GBM_midline‐clustered tumours had a poorer overall survival (OS) compared with the PXA‐clustered tumours (p = 0.030). LGG‐clustered cases had a significantly better survival than GBM_midline‐clustered tumours and glioblastoma RTK/mesenchymal‐clustered tumours. Only 13/21 (62%) of PXA‐clustered cases were BRAF V600E mutated. Most GBM_midline‐clustered cases were not located in the midline. GBM_midline‐clustered cases were characterised by PDGFRA amplification/mutation (73.3%), mutations of mismatch repair genes (40.0%), and all showed H3K27me3 and EZH1P loss, and an unmethylated MGMT promoter. Across the whole cohort, MGMT promoter methylation and wt TERT promoter were favourable prognosticators. Mismatch repair gene mutations were poor prognosticators and together with methylation class and MGMT methylation, maintained their significance in multivariate analyses. BRAF mutation was a good prognosticator in the PXA‐clustered tumours. Conclusion: Methylation profiling is a useful tool in the diagnosis and prognostication of AYA glioblastomas, and the methylation classes have distinct molecular characteristics. The usual molecular diagnostic criteria for adult IDHwt glioblastoma should be applied with caution within the AYA age group. [ABSTRACT FROM AUTHOR]

Current therapeutic options for acute kidney injury (AKI) are limited to the use of supportive measures and dialysis. A recent approach that has sparked great interest and gained enormous popularity is the implantation of stem cells to repair acutely damaged kidney organ. Hypoxia inducible factor-1α (HIF-1α) is effective in protecting the kidney from ischemia and nephrotoxicity. In this study, we investigated whether HIF-1α-modified adipose-derived stem cells (ASCs) had an enhanced protective effect on cisplatin-induced kidney injury in vivo. Cisplatin-induced AKI was established in nude mice. Our study demonstrated that HIF-1α-modified ASCs obviously promoted the recovery of renal function, ameliorated the extent of histologic injury and reduced renal apoptosis and inflammation, but HIF-1α-modified ASCs homed to kidney tissues at very low levels after transplantation. In addition, we also found that HIF-1α-modified ASCs significantly increased HO-1 expression in cisplatin-induced AKI in vivo. Thus, our study indicated HIF-1α-modified ASCs implantation could provide advanced benefits in the protection again AKI, which will contribute to developing a new therapeutic strategy for the treatment of AKI. [ABSTRACT FROM AUTHOR]

Purpose: Appropriate prescription of oral anticoagulants (OACs) and good patient adherence are essential to ensure optimal anticoagulation in patients with atrial fibrillation (AF). The aim of this study is to develop a mobile health tool to aid both clinicians and patients with AF in anticoagulation therapy. Methods: In this study, a novel anticoagulation management model integrating decision support and patient follow-up, the I-Anticoagulation, was developed based on a WeChat Mini Program. With this tool, the risks of stroke and bleeding in AF patients can automatically be calculated according to their characteristics. Anticoagulation regimens were recommended based on a trade-off analysis that balances stroke and bleeding risks according to recent clinical guidelines. A shared decision can be made with full communication between medical professionals and patients. Moreover, follow-up was also conducted using I-Anticoagulation. Results: A total of 120 AF patients receiving anticoagulants (40 received warfarin and 80 received non-vitamin K antagonist oral anticoagulants [NOACs]) were included in the pilot study. The incidence of thromboembolic events was 2.5% and 1.3%, and the rates of bleeding events were 22.5% and 13.8% in the warfarin and NOAC groups, respectively. Generally, self-reported adherence was high, and the satisfaction with anticoagulation was good in all patients with AF. Conclusion: Overall, the anticoagulation management model developed in this study could be involved in the full process of anticoagulation therapy in AF patients to improve rationality, adherence, and satisfaction in both medical professionals and patients. However, the usability, feasibility, and acceptability of the I-Anticoagulant-based anticoagulation management model need to be further assessed through well-designed random clinical trials. [ABSTRACT FROM AUTHOR]

We propose a novel “low-rank + dual” model for the matrix decomposition problems. Based on the unitarily invariant property of the Schatten p -norm, we prove that the solution of the proposed model can be obtained by an “ l ∞ + l 1 ” minimization problem, thus a simple and fast algorithm can be provided to solve our new model. Furthermore, we find that applying “ l ∞ + l 1 ” to any vector can achieve a shifty threshold on the values. Experiments on the simulation data, the real surveillance video database and the Yale B database prove the proposed method to outperform the state-of-the-art techniques. [ABSTRACT FROM AUTHOR]

The exact and explicit homoclinic solution of the undamped Helmholtz-Duffing oscillator is derived by a presented hyperbolic function balance procedure. The homoclinic solution of the self-excited Helmholtz-Duffing oscillator can also be obtained by an extended hyperbolic perturbation method. The application of the present homoclinic solutions to the chaos prediction of the nonautonomous Helmholtz-Duffing oscillator is performed. Effectiveness and advantage of the present solutions are shown by comparisons. [ABSTRACT FROM AUTHOR]

• The zigzag Trombe wall, a novel combined Trombe wall, was proposed here; • A well-designed experiment was conducted on the Trombe walls in winter days; • Parameters influencing the zigzag Trombe wall thermal performance were investigated; • Transient fluid flow and heat transfer of the zigzag Trombe wall were disclosed; • Zigzag Trombe wall could be applied for such poor solar energy regions. Solar energy building applications are gaining more attention due to their benefits in sustainable development, including energy conservation, cost reduction, and environmental protection. Present work proposed the zigzag Trombe wall, and its performance was investigated by on-site reduced-scale experiments and delicate CFD simulations, on a typical winter day in Wuhan, China. Unlike the traditional Trombe walls, our proposed zigzag Trombe wall has two sections, one of the sections comprises a southeast-facing window that provides both natural light and direct heat gain in the morning when promotion of heating efficiency is most needed; whereas the other consists of a southwest-facing Trombe wall with circulating vents that stores the afternoon sun's heat for redistribution during the relatively cold night hours. Here, fluid flow, heat distribution, and thermal comfort were introduced as key indices to investigate the performance of the zigzag Trombe wall around the whole typical day, regarding of the effects of the angle α and area ratio γ between two sections. Simulation results of the zigzag Trombe wall were compared with that of the classical Trombe wall, and which showed that this new one could effectively distribute heat throughout the day, especially in the morning period. This paper provides theoretical support and optimization ideas for the design and operation of the novel zigzag Trombe wall through a combination of experimental and numerical simulation methods. [ABSTRACT FROM AUTHOR]

Annular thermoelectric power generator has been increasingly considered in application of ambient energy harvesting owing to the advantages of simple structure and no pollution. To improve thermal stability and energy harvesting performance of this system, the latent heat of phase change materials to improve thermal management and the high thermal conductivity of the heat sink to enhance heat transfer with the ambient are harness to annular thermoelectric power generator. Motivated by this, a phase change material based annular thermoelectric energy harvester (PCM-ATEH) with fins is developed for ambient energy harvesting and its three-dimensional transient model is also built up through jointly with thermo-electric and phase change processes. This paper considers the influence of key parameters such as temperature fluctuation amplitude, temperature fluctuation period, height ratio of PCM and thermoelectric generator (TEG) and melting temperature on liquid fraction, temperature difference, voltage and power density. Moreover, the comparison of PCM-ATEH and PCM based thermoelectric energy harvester (PCM-TEH) with/without fins is further conducted in this study to explore thermal management and energy harvesting performance. The energy harvesting characteristics of PCM-ATEH with fins is developed concerning the combination of power generation of TEG and melting process of PCM. Based on the results, it is found that the temperature difference and power density of PCM-ATEH with fins vary periodically with the sinusoidal temperature boundary, and results show that increasing temperature fluctuation period is not always feasible. Additionally, the comparative results indicate that the peak power density and energy efficiency of PCM-ATEH with fins are increased by 0.126 W/m2 and 0.02 % compared with PCM-TEH with fins, and increased by 0.195 W/m2 and 0.041 % compared with PCM-ATEH without fins. The results of energy harvesting characteristics show that a maximum of 0.77$ per watt can be reached to power generation cost of PCM-ATEH with fins. This paper can provide theoretical guidance for thermal management and energy conversion of energy harvesting system. [ABSTRACT FROM AUTHOR]

Annular thermoelectric power generator has been increasingly considered in application of ambient energy harvesting owing to the advantages of simple structure and no pollution. To improve thermal stability and energy harvesting performance of this system, the latent heat of phase change materials to improve thermal management and the high thermal conductivity of the heat sink to enhance heat transfer with the ambient are harness to annular thermoelectric power generator. Motivated by this, a phase change material based annular thermoelectric energy harvester (PCM-ATEH) with fins is developed for ambient energy harvesting and its three-dimensional transient model is also built up through jointly with thermo-electric and phase change processes. This paper considers the influence of key parameters such as temperature fluctuation amplitude, temperature fluctuation period, height ratio of PCM and thermoelectric generator (TEG) and melting temperature on liquid fraction, temperature difference, voltage and power density. Moreover, the comparison of PCM-ATEH and PCM based thermoelectric energy harvester (PCM-TEH) with/without fins is further conducted in this study to explore thermal management and energy harvesting performance. The energy harvesting characteristics of PCM-ATEH with fins is developed concerning the combination of power generation of TEG and melting process of PCM. Based on the results, it is found that the temperature difference and power density of PCM-ATEH with fins vary periodically with the sinusoidal temperature boundary, and results show that increasing temperature fluctuation period is not always feasible. Additionally, the comparative results indicate that the peak power density and energy efficiency of PCM-ATEH with fins are increased by 0.126 W/m2 and 0.02 % compared with PCM-TEH with fins, and increased by 0.195 W/m2 and 0.041 % compared with PCM-ATEH without fins. The results of energy harvesting characteristics show that a maximum of 0.77$ per watt can be reached to power generation cost of PCM-ATEH with fins. This paper can provide theoretical guidance for thermal management and energy conversion of energy harvesting system. [ABSTRACT FROM AUTHOR]

Adhesion G protein-coupled receptors (aGPCRs) are evolutionarily ancient receptors involved in a variety of physiological and pathophysiological processes. Modulators of aGPCR, particularly antagonists, hold therapeutic promise for diseases like cancer and immune and neurological disorders. Hindered by the inactive state structural information, our understanding of antagonist development and aGPCR activation faces challenges. Here, we report the cryo-electron microscopy structures of human CD97, a prototypical aGPCR that plays crucial roles in immune system, in its inactive apo and G13-bound fully active states. Compared with other family GPCRs, CD97 adopts a compact inactive conformation with a constrained ligand pocket. Activation induces significant conformational changes for both extracellular and intracellular sides, creating larger cavities for Stachel sequence binding and G13 engagement. Integrated with functional and metadynamics analyses, our study provides significant mechanistic insights into the activation and signaling of aGPCRs, paving the way for future drug discovery efforts. [Display omitted] • Cryo-EM structures of human CD97 in both inactive and active states are studied • We elucidate the binding modes of the Stachel sequence of aGPCR in both states • We uncover the conformational transitions involved in aGPCR activation • We decode the conserved activation-related motifs of aGPCRs Mao et al. use cryo-EM to uncover adhesion G protein-coupled receptor (aGPCR) intricacies. These ancient receptors, crucial in physiology, offer therapeutic potential for diseases like cancer. Hindered by the knowledge gap in structural information, we face challenges in understanding antagonist development and aGPCR activation The research unveils cryo-EM structures of CD97 in both inactive and fully active states. CD97, unlike other GPCRs, has a compact inactive form. Activation induces changes, creating cavities for binding and engagement. Integrated analyses provide insights, paving the way for aGPCR modulation in drug discovery. Cryo-EM structures of human CD97 in its inactive apo and G13-bound fully active states provide mechanistic insights into the activation and drug development of aGPCRs. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the growth and fixed points of solutions of higher-order linear differential equations in the unit disc. We extend the coefficient conditions to a type of one-constant-control coefficient comparison and obtain the same estimates of iterated order of solutions. We also obtain better estimates by providing a precise value of iterated order of solution instead of a range of that in the case of coefficient characteristic function comparison. Moreover, we utilize iteration to investigate and estimate the fixed points of solutions' arbitrary-order derivatives with higher-order equations f (k) + A k − 1 (z) f (k − 1) + ⋯ + A 1 (z) f ′ + A 0 (z) f = 0 and provide a concise method to judge if the items generated by the iteration do not vanish identically and ensure the iteration proceeds. Our results are an improvement over those by B. Belaïdi, T. B. Cao, G. W. Zhang and A. Chen. [ABSTRACT FROM AUTHOR]

Main observation and conclusion: Transition metal‐rare earth oxide catalysts had the ability to catalyze ammonia decomposition according to recent years' scientific reports. However, most of those catalysts had their own limitations: the catalytic activity was poor, and/or the active species could not clearly be identified. Here we report the CoaSmbOx catalysts with good dispersion, controllable content, and excellent catalytic performance for ammonia decomposition. The various content catalysts were synthesized by aerosol‐assisted self‐assembly approach. These catalysts had high dispersion and great morphology according to the images of the transmission electron microscope (TEM) and the scanning electron microscope (SEM). The temperature‐programmed reduction by hydrogen (H2‐TPR) and in‐situ X‐ray diffraction (XRD) results indicated that the interaction between cobalt oxide and samarium oxide influenced the redox properties of cobalt oxide. Combined with in‐situ Raman, we found that Co0 was an active species of the CoaSmbOx catalysts in ammonia decomposition. Moreover, the temperature‐programmed desorption of NH3 (NH3‐TPD) data illustrated that the addition of Sm was beneficial to the adsorption of NH3. In general, we successfully obtained the CoaSmbOx catalyst with high activity and good stability. More importantly, we have identified the structure‐function relationship of catalysts by exploring the active species in the reaction process. [ABSTRACT FROM AUTHOR]

The spontaneous depurination of genomic DNA occurs frequently and generates apurinic/pyrimidinic (AP) site damage that is mutagenic or lethal to cells. Error-prone DNA polymerases are specifically responsible for the translesion synthesis (TLS) of specific DNA damage, such as AP site damage, generally with relatively low fidelity. The Y-family DNA polymerases are the main error-prone DNA polymerases, and they employ three mechanisms to perform TLS, including template-skipping, dNTP-stabilized misalignment, and misincorporation-misalignment. The bypass mechanism of the dinB homolog (Dbh), an archaeal Y-family DNA polymerase from Sulfolobus acidocaldarius, is unclear and needs to be confirmed. In this study, we show that the Dbh primarily uses template skipping accompanied by dNTP-stabilized misalignment to bypass AP site analogs, and the incorporation of the first nucleotide across the AP site is the most difficult. Furthermore, based on the reported crystal structures, we confirmed that three conserved residues (Y249, R333, and I295) in the little finger (LF) domain and residue K78 in the palm subdomain of the catalytic core domain are very important for TLS. These results deepen our understanding of how archaeal Y-family DNA polymerases deal with intracellular AP site damage and provide a biochemical basis for elucidating the intracellular function of these polymerases. [ABSTRACT FROM AUTHOR]

Abstract: Total generalized variation (TGV) regularization model is one of the most effective methods for denoising and eliminating staircase effect. However, the TGV regularization model tends to blur edges as the existence of high-order derivative. In order to avoid the staircase effect while alleviating the edge blurring, an iterative reweighted TGV based Poisson noise removal model is presented under the assumption that each pixel of noisy image follows a Poisson distribution. The weight function incorporated in the TGV regularization term is derived from the expectation maximization (EM) algorithm. We design a new iterative weighted primal–dual algorithm, which is an improvement of the classic iterative reweighted algorithm. Numerical experimental results show the better performance of our model in removing noise effectively while preserving edges and eliminating staircase effect. [Copyright &y& Elsevier]

Objective. To observe the protective effect of AC-YVAD-CMK on sepsis-induced acute kidney injury in mice and to explore its possible mechanisms primarily. Methods. Eighteen male C57BL/6 mice were randomly divided into sham-operated group (Control), cecal ligation and puncture group (CLP), and CLP model treated with AC-YVAD-CMK group (AC-YVAD-CMK) (n = 6 in each group). Mice were sacrificed at 24 h after operation, and blood and kidney tissue samples were collected for analyses. Histologic changes were determined microscopically following HE staining. The expression of Ly-6B and CD68 was investigated using immunohistochemistry. Serum concentrations of creatinine (sCR) and blood urea nitrogen (BUN) were measured. Serum levels of interleukin-1β (IL-1β), interleukin-18 (IL-18), TNF-α, and interleukin-6 (IL-6) were determined by ELISA. The expressions of Caspas-1, NLRP-1, IL-1β, and IL-18 in renal tissues were investigated using Western blot. Immunofluorescence staining was used to detect the expression of GSDMD protein in renal tissues. Results. AC-YVAD-CMK treatment significantly alleviates sepsis-induced acute kidney injury, with decreased histological injury in renal tissues, suppresses the accumulation of neutrophils and macrophages in renal tissues, and decreased sCR and BUN level (P < 0.05). Attenuation of sepsis-induced acute kidney injury was due to the prohibited production of inflammatory cytokines and decrease expression of Caspas-1, NLRP-1, IL-1β, and IL-18 in renal tissues. In addition, AC-YVAD-CMK treatment significantly reduced the expression of GSDMD in renal tissues compared to those observed in controls (P < 0.05). Conclusions. We demonstrated a marked renoprotective effect of caspase-1-inhibitor AC-YVAD-CMK in a rat model of sepsis by inhibition of pyroptosis. [ABSTRACT FROM AUTHOR]

Convection resonance could be significant for strengthening heat and mass transfer rates in enclosure flows, such as electronic cooling, built air environment and green energy harvest. This paper presented a numerical investigation on the coupled heat and moisture transport and resonance phenomena in enclosures packed with discrete porous media, where natural convection dominated, mixing convection, and forced convection dominated domains could be covered. Various physical parameters were extensively investigated, including buoyancy ratio (−10 ≤ Br ≤ 10), permeability (10−6 ≤ Da ≤ 101), Richardson number (10−1 ≤ Ri ≤ 5), Reynolds number (50 ≤ Re ≤ 1000), enclosure tilting angle (0° ≤ Φ ≤ 180°), thermal conductivity (0.1 ≤ Kr ≤ 10), and frequency (10−2 ≤ ω ≤ 5). Present results showed that in a vertical enclosure, reduction of porous medium permeability and promotion of the ratio of Richardson number to floating force could enhance heat and mass transfer rates. In an inclined enclosure, the effect of buoyancy and inclination angle on heat and mass transfer processes and rates exhibits a centrally symmetric distribution. In addition, a dense porous media and cooperative heat and mass buoyancy force ratio were beneficial to reducing the total entropy production. Finally, the transient heat and moisture transport and resonance phenomena in discrete distributed porous media were investigated. The system exhibits significant self-excited oscillations at ω = 100, being evident whatever sparse or dense porous media. Heat and mass transfer pulse amplitude in a periodically varying heat source enclosure decays with increasing porous medium thermal conductivity ratio, whereas it increases with increasing buoyancy ratio and Reynolds numbers. The most significant heat and moisture resonance occurs in a mixed convection system with Da = 10 and Br = 4. Present oscillation and resonance researches could contribute to the development of electronic cooling or built ventilation with much low or free cost of thermal management. • Heat and moisture transports inside in an inclined porous enclosure were modelled. • Transient, oscillatory, and resonant states were observed for mixed convections. • Reduction of porous permeability and promotion of Ri and Br enhanced transport rates. • Dense porous media and cooperative Br aided entropy production in inclined enclosure. • Self-excited oscillation and resonance were fully analyzed by various parameters. [ABSTRACT FROM AUTHOR]

• A novel coaxial condensing heat pipe applied in the solar CCHP/PVT system was proposed. • Thermal, electrical and exergy efficiencies of the solar CCHP/PVT system were defined. • Proposed CCHP/PVT system has better performance in thermal and electrical efficiencies. • Current theoretical models and codes were well validated by former experiments and results. • CCHP/PVT was favored for solar exploitation, particularly in the solar energy poor regions. Heat pipes offer tremendous potential for utilization in the energy and construction industries due to their excellent heat transmission efficiency. The current study involved the development of a theoretical model for thermal transport in a coaxial condensing heat pipe (CCHP) connected with solar photovoltaic and thermal (PVT) systems. Subsequently, parameter studies were conducted to analyze their impact on system performance, including irradiation intensity, surrounding temperature, inlet temperature, mass flow rate and PV coverage factor. In addition, temperature variation, thermal and electrical conversion capabilities of the CCHP/PVT system on typical days were discussed utilizing meteorological conditions in Wuhan city as inputs for the analysis. Our findings showed that the morning is when thermal efficiency is at its highest across the seasons, and it remained between 50% and 55%. Compared to natural cooling and conventional heat pipe cooling, the CCHP/PVT system reduced the temperature of the PV panels by approximately 30.3% and 16.3%, respectively. The proposed CCHP/PVT system has a respectively 14.4% and 5.2% enhancement in thermal and electrical efficiencies in comparison with those conventional heat pipes. Here, theoretical results agree well with former published ones, with average errors of no more than 10%. Our parametric investigations were then put into practice to assess the overall performance and to serve as a theoretical foundation for later development. It was really beneficial to boost the efficiency of solar energy utilization in the Yangtze River, China, where solar potentials were relatively poor than north western China. [ABSTRACT FROM AUTHOR]

Abstract: Pigment epithelium-derived factor (PEDF) recombinant protein has been investigated in many kinds of solid tumors due to its potent antiangiogenic activity. However, the complexity of protein purification, instability of recombinant protein and requirement of repeated injections are obstacles for the recombinant PEDF therapy for solid tumors. We successfully synthesized polyethyleneglycol–polyetherimide (PEG–PEI) and cRGD–PEG–PEI which was coupled with a cyclic RGD peptide, a special ligand for integrin αvβ3 receptor, as the vehicle for PEDF gene therapy in this study. In vitro, the competitive binding assay showed that cRGD contributed to the enhanced gene transfection efficiency of PEG–PEI in human umbilical vein endothelial cells (HUVECs). PEDF gene delivered by cRGD–PEG–PEI apparently suppressed growth of tumor with a 67.4% reduction and decreased microvessel density in nude mice bearing SW620 human colorectal xenografts. Accordingly, SW620 tumors from cRGD–PEG–PEI/PEDF–pcDNA3.1 (+)-treated mice expressed more PEDF than that of the control groups. Our study demonstrated that cRGD–PEG–PEI transported the PEDF gene into endothelia cells more efficiently than PEG–PEI, resulting in more effective inhibitory effects on tumor growth by anti-angiogenesis. Therefore, for the first time, we have explored an effective non-viral vehicle for PEDF gene therapy by targeting endothelial cells. [Copyright &y& Elsevier]

Abstract: Aim of the study: To evaluate the anti-diabetic effects of the total flavonoids of Selaginella tamariscina (Beauv.) Spring (TFST), and to explore the pertinent mechanism. Materials and methods: High fat diet and STZ (35mg/kg) induced diabetic rats were administered with TFST at graded oral doses (100, 200 and 400mg/kg/day, ig.) for 8weeks. A range of parameters, including blood glucose and lipid, serum insulin and glucagon, glucose tolerance, were tested to evaluate its anti-diabetic effects. The determination of protein expression of peroxisome proliferator activated receptor γ (PPAR-γ) in adipose tissue and insulin receptor substrate 1 (IRS-1) in hepatic and skeletal muscle tissues was used to study the mechanism of TFST. Moreover, the preliminary study of TFST on the antioxidant activity was performed. Results: The TFST possessed anti-diabetic activities as shown by the decreased serum levels of fast blood glucose (FBG), glycosylated hemoglobulin A1C (HbA1c), triglyceride (TG), total cholesterol (TC), free fatty acid (FFA), low density lipoprotein-cholesterol (LDL-C) and glucagon, as well as increased serum levels of high density lipoprotein-cholesterol (HDL-C), insulin and C-peptide. TFST also improved the oral glucose tolerance test (OGTT) to a certain degree. Furthermore, TFST increased the protein expression of PPAR-γ in adipose tissue, and increased the protein expressions of IRS-1 in hepatic and skeletal muscle tissues. These benefits were associated with increased superoxide dismutase (SOD) and decreased malondialdehyde (MDA) in serum. Conclusions: TFST exert beneficial effects on hyperglycosemia and hyperlipoidemia in diabetic rats possibly through regulating the levers of PPAR-γ in adipose tissue and IRS-1 in hepatic and skeletal muscle tissues. [Copyright &y& Elsevier]

Abstract: In this study we investigated whether ethanol could play neuroprotective effects against ischemic brain injury and the related mechanism. Cresyl violet staining results demonstrated that moderate dose of ethanol administered intracerebroventricularly (i.c.v.) had neuroprotective effect against ischemia–reperfusion induced neuronal cell death. Ethanol also inhibited the phosphorylation of JNK3 induced by cerebral ischemia–reperfusion. Three separate drugs, NS3763 (the selective antagonist of GluR5), GluR5 antisense oligodeoxynucleotides (AS-ODNs) and Bicuculline (an antagonist of GABA receptors), were found to inhibit the neuroprotective effect of ethanol. Moreover, the GABA receptor agonist muscimol could attenuate the JNK3 phosphorylation. Taken together, the results suggest that during ischemia–reperfusion ethanol may activate presynaptic GluR5-KA and postsynaptic GABA receptors continuously, and the activation of GABA receptors inhibits the JNK3 signal pathway. The results show a novel potential mechanism underlying ethanol protective effects. [Copyright &y& Elsevier]

Abstract: Based on fractal theory, different two-dimensional fractal structures were constructed to simulate the practical porous media. Effective thermal conductivity for porous media was calculated by means of the finite volume method. Theoretical analysis of thermal response in the porous media under various heating conditions was performed with a multi-layer hyperbolic heat conduction model with volumetric heat generation. The results obtained in this paper indicate that pore size and micro distribution have a far-reaching impact on the heat conduction in porous media. If we assumed that both the thermal conductivity and the heat capacity of the solid phase is larger than those of liquid phase, decreasing the pore size and porosity is helpful to enhance the heat transfer in porous media and the peak of temperature increases with pore size and porosity. With the same pore size and porosity, the effect of the pore micro-geometric distribution on heat conduction in porous media is obvious. The method presented in this paper may suggest a valuable approach to theoretically evaluate the effect of pore micro-geometric structure on heat conduction in porous media. [Copyright &y& Elsevier]

Abstract: We synthesized a series of novel small molecules, 2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine derivatives, by tandem reduction-oxirane opening of 2-nitroaroxymethyloxiranes in moderate or excellent yields. We investigated the effects of all of the compounds on HUVEC apoptosis and A549 cell growth. The results showed that 6,8-dichloro-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine was the most effective small molecule in promoting HUVEC apoptosis and inhibiting A549 cell proliferation, but 6-amino-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine could remarkably inhibit HUVEC apoptosis and might induce the formation of microvessel. [Copyright &y& Elsevier]

Cardiac fibrosis is involved in adverse cardiac remodeling and heart failure, which is the leading cause of deteriorated cardiac function. Accumulative evidence has elucidated that microRNAs (miRNAs) play important roles in the pathogenesis of cardiac fibrosis. However, the exact molecular mechanism underlying miR-144 in cardiac fibrosis remains unknown. In the present study, a transverse aortic constriction (TAC) mouse model and angiotensin II (Ang II)-induced cardiac fibroblasts (CFs) were constructed in order to investigate the expression levels of miR-144. It was demonstrated that miR-144 was significantly downregulated following pathological stimuli. CFs infected with miR-144 mimics were then used to test the effect of miR-144 on CF activation in vitro. The results revealed that overexpression of miR-144 led to a dramatically decreased proliferation and migration ability in CFs, as well as the transformation from fibroblasts to myofibroblasts, which was characterized by the decreased expression of collagen-I, collagen-III, CTGF, fibronectin and α-SMA. By contrast, such effects could be reversed by miR-144 knockdown. Mechanistically, the bioinformatics analysis and luciferase reporter assay in the present study demonstrated that cAMP response element-binding protein (CREB) was a direct target of miR-144, and the expression of CREB was attenuated by miR-144. The results of the present study demonstrated that miR-144 played a key role in CF activation, partially by targeting CREB, which further suggested that the overexpression of miR-144 may be a promising strategy for the treatment of cardiac fibrosis. [ABSTRACT FROM AUTHOR]

Electronic effects on the central carbon atom of carbone, generated by the replacement of the SIV ligand of carbodisulfane (CDS) with other chalcogen ligands (Ph2E, E=S or Se), were investigated. The carbones Ph2E→C←SPh2(NMe) [E=S( 1) or Se( 2)] were synthesized from the corresponding salts, and their molecular structures and electronic properties were characterized. The carbone 2 is the first carbone containing selenium as the coordinated atom. DFT calculations revealed the electronic structures of 1 and 2, which have two lone pairs of electrons at the carbon center. The trend in HOMO energy levels, estimated by cyclic voltammetry measurements, for the carbones and CDS follows the order of 2> 1>CDS. Analysis of a doubly protonated dication and trication complex revealed that the central carbon atom of 2 behaves as a four-electron donor. [ABSTRACT FROM AUTHOR]

Electronic effects on the central carbon atom of carbone, generated by the replacement of the SIV ligand of carbodisulfane (CDS) with other chalcogen ligands (Ph2E, E=S or Se), were investigated. The carbones Ph2E→C←SPh2(NMe) [E=S( 1) or Se( 2)] were synthesized from the corresponding salts, and their molecular structures and electronic properties were characterized. The carbone 2 is the first carbone containing selenium as the coordinated atom. DFT calculations revealed the electronic structures of 1 and 2, which have two lone pairs of electrons at the carbon center. The trend in HOMO energy levels, estimated by cyclic voltammetry measurements, for the carbones and CDS follows the order of 2> 1>CDS. Analysis of a doubly protonated dication and trication complex revealed that the central carbon atom of 2 behaves as a four-electron donor. [ABSTRACT FROM AUTHOR]

In the 2016, WHO classification of tumors of the central nervous system, isocitrate dehydrogenase (IDH) mutation is a main classifier for lower grade astrocytomas and IDH‐mutated astrocytomas is now regarded as a single group with longer survival. However, the molecular and clinical heterogeneity among IDH mutant lower grade (WHO Grades II/III) astrocytomas have only rarely been investigated. In this study, we recruited 160 IDH mutant lower grade (WHO Grades II/III) astrocytomas, and examined PDGFRA amplification, CDKN2A deletion and CDK4 amplification by FISH analysis, TERT promoter mutation by Sanger sequencing and ATRX loss and p53 expression by immunohistochemistry. We identified PDGFRA amplification, CDKN2A homozygous deletion and CDK4 amplification in 18.8%, 15.0% and 18.1% of our cohort respectively, and these alterations occurred in a mutually exclusive fashion. PDGFRA amplification was associated with shorter PFS (P = 0.0003) and OS (P < 0.0001). In tumors without PDGFRA amplification, CDKN2A homozygous deletion or CDK4 amplification was associated with a shorter OS (P = 0.035). Tumors were divided into three risk groups based on the presence of molecular alterations: high risk (PDGFRA amplification), intermediate risk (CDKN2A deletion or CDK4 amplification) and low risk (neither CDKN2A deletion and CDK4 amplification nor PDGFRA amplification). These three risk groups were significantly different in overall survival with mean survivals of 40.5, 62.9 and 71.5 months. The high‐risk group also demonstrated a shorter PFS compared to intermediate‐ (P = 0.036) and low‐risk (P < 0.0001) groups. One limitation of this study is the relatively short follow‐up period, a common confounding factor for studies on low‐grade tumors. Our data illustrate that IDH mutant lower grade astrocytomas is not a homogeneous group and should be molecularly stratified for risk. [ABSTRACT FROM AUTHOR]

Background: Omega 3 polyunsaturated fatty acid (Omega-3PUFA) is one of the essential nutrients for human body involved in intracellular metabolic regulation and cell signaling. Previous studies have shown that Omega-3PUFA is involved in the pathogenesis of digestive system tumors, including colorectal cancer (CRC), however, the effects of Omega-3PUFA on CRC has not been fully elucidated. In the current study, we evaluated whether Omega-3PUFA can alleviate N-methyl-N-nitrosourea(MNU) induced CRC in a rat model and illustrated the potential mechanism. Methods: The effects of Omga-3PUFA on MNU-induced colorectal cancer in rats were analyzed by in vivo experiments. The viability, apoptosis, colony formation and invasion of CRC cells treated with Omga-3PUFA were detected by CCK8, flow cytometry, clone formation assay and transwell invasion assay. The expression of apoptosis-related proteins in CRC cells treated with Omga-3PUFA was detected by Western blotting. Finally, after adding PI3K activator, the viability, apoptosis and protein expression of CRC cells treated with Omga-3PUFA were detected by CCK8, flow cytometry and Western blotting. Results: Our results showed that Omega-3PUFA attenuated MNU-induced CRC in rats and inhibited AKT/Bcl-2 signaling in rats. In addition, Omega-3PUFA inhibited CRC cell proliferation and induces CRC cell apoptosis. Moreover, Omega-3PUFA inhibited CRC cell colony formation and invasion, and inhibited PI3K/AKT/Bcl-2 signaling in CRC cells. Furthermore, The effects of Omega-3PUFA on cell proliferation and apoptosis were inhibited by blocking PI3K/AKT signaling. Conclusion: Omega-3PUFA can attenuate MNU-induced colorectal cancer in rats by blocking PI3K/AKT/Bcl-2 signaling, which suggests that Omega-3PUFA may be a potent agent for CRC treatment. [ABSTRACT FROM AUTHOR]

Background: Porcine infectious pleuropneumonia caused by Actinobacillus pleuropneumoniae (App) is one of the most serious infectious diseases in pigs and has brought huge economic losses to the world pig industry. The aim of this trial was to evaluate the effect of enteric‐coated tilmicosin granule in the treatment and control of artificial infection of App. Methods: Sixty Duroc and Yorkshire crossbred pigs (50 of which were artificially infected) were divided into six groups: BCG (Blank control group), ICG (Infection‐only control group), HDG (High‐dose enteric‐coated tilmicosin granules), MDG (Medium‐dose enteric‐coated tilmicosin granules), LDG (Low‐dose enteric‐coated tilmicosin granules) and TPG (Tilmicosin premix drug control group). The cure rate, mortality, clinical respiratory score, body temperature score, weight gain, lung score and so on were recorded. Results: The cure rate of HDG and MDG was as high as 90%, the mortality was 10%, and the clinical signs recovered quickly. Conclusion: The results showed that enteric‐coated tilmicosin granules had obvious therapeutic effect on artificial infection, which could reduce the damage caused by the disease and reduce the mortality. [ABSTRACT FROM AUTHOR]

Background: Dendritic cell-associated C-type lectin-1 (Dectin-1) receptor has been reported to be involved in neuroinflammation in Alzheimer's disease and traumatic brain injury. The present study was designed to investigate the role of Dectin-1 and its downstream target spleen tyrosine kinase (Syk) in early brain injury after ischemic stroke using a focal cortex ischemic stroke model.Methods: Adult male C57BL/6 J mice were subjected to a cerebral focal ischemia model of ischemic stroke. The neurological score, adhesive removal test, and foot-fault test were evaluated on days 1, 3, 5, and 7 after ischemic stroke. Dectin-1, Syk, phosphorylated (p)-Syk, tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) expression was analyzed via western blotting in ischemic brain tissue after ischemic stroke and in BV2 microglial cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury in vitro. The brain infarct volume and Iba1-positive cells were evaluated using Nissl's and immunofluorescence staining, respectively. The Dectin-1 antagonist laminarin (LAM) and a selective inhibitor of Syk phosphorylation (piceatannol; PIC) were used for the intervention.Results: Dectin-1, Syk, and p-Syk expression was significantly enhanced on days 3, 5, and 7 and peaked on day 3 after ischemic stroke. The Dectin-1 antagonist LAM or Syk inhibitor PIC decreased the number of Iba1-positive cells and TNF-α and iNOS expression, decreased the brain infarct volume, and improved neurological functions on day 3 after ischemic stroke. In addition, the in vitro data revealed that Dectin-1, Syk, and p-Syk expression was increased following the 3-h OGD and 0, 3, and 6 h of reperfusion in BV2 microglial cells. LAM and PIC also decreased TNF-α and iNOS expression 3 h after OGD/R induction.Conclusion: Dectin-1/Syk signaling plays a crucial role in inflammatory activation after ischemic stroke, and further investigation of Dectin-1/Syk signaling in stroke is warranted. [ABSTRACT FROM AUTHOR]

In this article, 23 compounds (6 and 7a–7v) were prepared and evaluated for their in vitro α-glucosidase inhibitory activity. The compounds 7d, 7f, 7i, 7n, 7o, 7r, 7s, 7u, and 7v displayed the α-glucosidase inhibition activity with IC50 values ranging from 1.68 to 7.88 µM. Among all tested compounds, 7u was found to be the most efficient, being 32-fold more active than the standard drug acarbose, which significantly attenuated postprandial blood glucose in mice. In addition, the compound 7u also induced the fluorescence quenching and conformational changes of enzyme, by forming α-glucosidase–7u complex in a mixed inhibition type. The thermodynamic constants recognised the interaction between 7u and α-glucosidase and was an enthalpy-driven spontaneous exothermic reaction. The synchronous fluorescence and CD spectra also indicate that the compound 7u changed the enzyme conformation. The findings identify the binding interactions between new ligands and α-glucosidase and reveal the compound 7u as a potent α-glucosidase inhibitor. [ABSTRACT FROM AUTHOR]

This study was aimed to evaluate the anti-inflammatory potential of AG on lipopolysaccharide (LPS) -induced liver injury and investigate the underlying mechanism. Administration of LPSs in the rat produced rat liver injury model which was ascertained at histological and molecular levels. Those models were treated with a range of doses of LPSs (0.5, 1.0 and 1.5 mg/kg body weight), followed by measurement physical parameter and function of the liver. Within the max treatment doses, no toxicity was shown but protective effects of AG were evidenced by regulation of physical parameters and functions of the liver. Interestingly, nuclear factor kappa B (NF-κB) levels and inflammatory factors were down-regulated by AG. Furthermore, the histopathological analysis demonstrated that AG promoted recovery from dysfunction of liver tissue in the rats, which was further confirmed by observing expression changes of inflammation-associated proteins. Particularly, alteration in the PI3K/AKT and JAK2/STAT3 signalling pathway protein expression were regulated by AG in a dose-dependent manner, indicating the mechanism underlying the relief effect of AG in liver injury. Our study demonstrated the potential of AG in the management of complications related to liver injury. [ABSTRACT FROM AUTHOR]

Considers the value of an integrative traditional and modern scientific approach to developing new treatments for dementia. Role of medicinal plants for dementia therapy; Details on relevant phytochemical and pharmacological research; Contribution of phytochemicals to understanding disease mechanisms; Information on integrative research strategies.

Marek's disease (MD) is an infectious malignant T-cell lymphoma proliferative disease caused by Marek's disease virus (MDV). In recent years, the emergence of very virulent (vv) and/or very virulent plus (vv +) strains of MDV in the field has been suggested as one of the causes of vaccination failure. The pathogenicity of the MDV strain GX18NNM4, isolated from a clinical outbreak in a broiler breeder flock that was vaccinated with CVI988/Rispens, was investigated. In the vaccination-challenge test, GX18NNM4 was able to break through the protections provided by the vaccines CVI988 and 814. It also significantly reduced body weight gain and caused marked gross lesions and a large area of infiltration of neoplastic lymphocyte cells in the heart, liver, pancreas, etc. of the infected birds. In addition, the expressions of programmed death 1 (PD-1) and its ligand, programmed death ligand 1 (PD-L1), in the spleens and cecal tonsils (CTs) of the unvaccinated challenged birds were significantly increased compared to those in the vaccinated challenged birds, indicating that the PD-1/PD-L1 pathway is related to immune evasion mechanisms. The results showed that the GX18NNM4 strain could cause severe immunosuppression and significantly decrease the protections provided by the current commercial vaccines, thus showing GX18NNM4 to be a vv + MDV strain. [ABSTRACT FROM AUTHOR]

The recently captured fullerene #6094C68 was found to exhibit a more aromatic character than originally assumed via density functional theory calcu-lations. Such an inconsistency was attributed to the unexpected triplet ground state of pristine #6094C68 The equilibrium concentrations of #6094C68 isomeric system reveal that mmC6s is thermodynamically favorable at elevated temperatures with respect to the fiillerene formation. The regioselective chlorination process of the open-shell C68 was discussed as well to elucidate the formation of octachlorinated derivative C68Cl8experimentally. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRs) were involved in numerous cardiovascular diseases, especially ischemic heart diseases, but the miR changes during cardiac ischemia–reperfusion (I/R) injury following sevoflurane (SEV) preconditioning are still unknown. This study aims to investigate the effect of miR‐874 on cardiac I/R injury in mouse models pretreated with SEV. Following establishment of mouse models with myocardial I/R injury, mice were pretreated with SEV. The functional mechanism of miR‐874 in I/R injury was explored when miR‐874 and the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway were inhibited. Terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP biotin nick‐end labeling (TUNEL) staining was used to detect cardiomyocyte apoptosis and dual luciferase reporter gene assay to identify the targeting relationship between miR‐874 and STAT3. Expression of the JAK2/STAT3 signaling pathway and apoptosis‐related genes was determined. Initially, upregulated miR‐874 was observed in I/R mice. Then, miR‐874 inhibition improved cardiac function of I/R mice, inhibited cardiomyocyte apoptosis (also shown as decreased Bcl‐2 associated X protein B [Bax] and increased B‐cell lymphoma‐2 [Bcl‐2]), and activated the JAK2/STAT3 signaling pathway. STAT3, a target gene of miR‐874, was upregulated following miR‐874 inhibition. Finally, we also observed that the effect of miR‐874 was lost when the JAK2/STAT3 signaling pathway was blocked. The findings indicate miR‐874 as a contributory role in cardiac I/R injury, with miR‐874 inhibition alleviating cardiac I/R injury in mice following SEV pretreatment by targeting STAT3 through the JAK2/STAT3 signaling pathway. The findings indicate microRNA (miR)‐874 as a contributory role in cardiac ischemia–reperfusion injury (I/R) injury, with miR‐874 inhibition alleviating cardiac I/R injury in mice following sevoflurane pretreatment by targeting signal transducer and activator of transcription 3 (STAT3) through the Janus kinase 2 (JAK2)/STAT3 signaling pathway. [ABSTRACT FROM AUTHOR]

We propose programed potential modulation strategies to balance the ion intercalation/deintercalation, surface tailoring and bubbling dispersion processes in the electrochemical exfoliation of graphite, resulting in high-quality graphene with high crystallinity, low oxidation degree, uniform size distribution and few layers. [ABSTRACT FROM AUTHOR]

Lithium metal anodes suffer from poor cycling stability and potential safety hazards. To alleviate these problems, Li thin‐film anodes prepared on current collectors (CCs) and Li‐free types of anodes that involve direct Li plating on CCs have received increasing attention. In this study, the atomic‐scale design of Cu‐CC surface lithiophilicity based on surface lattice matching of the bcc Li(110) and fcc Cu(100) faces as well as electrochemical achievement of Cu(100)‐preferred surfaces for smooth Li deposition with a low nucleation barrier is reported. Additionally, a purposely designed solid–electrolyte interphase is created for Li anodes prepared on CCs. Not only is a smooth planar Li thin film prepared, but a uniform Li plating/stripping on the skeleton of 3D CCs is achieved as well by high utilization of the surface and cavities of the 3D CCs. This work demonstrates surface electrochemistry approaches to construct stable Li metal–electrolyte interphases towards practical applications of Li anodes prepared on CCs. Get in touch with lithium: The generation of surface lithiophilicity on planar and 3D Cu hosts for Li metal anodes is reported. Enabled by a lattice matching of Cu(100) and Li(110), smooth deposition of Li thin films and the creation of ultra‐smooth ultra‐thin SEI on the Cu hosts is made possible. This allows a high utilization of not only the surface but also cavities of the Cu hosts. [ABSTRACT FROM AUTHOR]

Lithium metal anodes suffer from poor cycling stability and potential safety hazards. To alleviate these problems, Li thin‐film anodes prepared on current collectors (CCs) and Li‐free types of anodes that involve direct Li plating on CCs have received increasing attention. In this study, the atomic‐scale design of Cu‐CC surface lithiophilicity based on surface lattice matching of the bcc Li(110) and fcc Cu(100) faces as well as electrochemical achievement of Cu(100)‐preferred surfaces for smooth Li deposition with a low nucleation barrier is reported. Additionally, a purposely designed solid–electrolyte interphase is created for Li anodes prepared on CCs. Not only is a smooth planar Li thin film prepared, but a uniform Li plating/stripping on the skeleton of 3D CCs is achieved as well by high utilization of the surface and cavities of the 3D CCs. This work demonstrates surface electrochemistry approaches to construct stable Li metal–electrolyte interphases towards practical applications of Li anodes prepared on CCs. [ABSTRACT FROM AUTHOR]

Hepatocarcinoma is one of the most lethal malignancy haunting the Chinese population, which is partially due to the difficulties in diagnosis at an early stage. The search for a biomarker that could signify the presence and progress of hepatocarcinoma is never ended. MicroRNAs are 22-nt RNAs that could bind to 3′ UTR of target mRNAs, mediating degradation of mRNAs or inhibiting the translation. Although much has been investigated, the role of miR-124 in hepatocarcinoma remained elusive. We first detected aberrant expression level of miR-124 in HCC tissues of 112 patients. By exploring the clinical parameters, we found a significantly inverse correlation between miR-124 level and TNM stages. Consistent with this, the survival analysis indicated the association of low miR-124 with longer survival time. Subsequent forced expression miR-124 resulted in reduced cell viability of Hep3B and SMMC-7221, which cell lines have high and low background expression of miR-124, respectively. TargetScan prediction rendered a subset of target candidates, which were selected for experimental validation, KLF4 was subject to luciferase assay. Ectopic expression of KLF4 increased the sphere formation ability and CD44/133-positive cell numbers, which can be reversed by abundant expression of miR-124, suggesting that KLF4 is a functional target of miR-124 in tumourigenesis and cancer progression of HCC. [ABSTRACT FROM AUTHOR]

Oral cancer remains a major public concern with considerable socioeconomic impact in the world, especially in southeast Asia. Despite substantial advancements have been made in treating oral cancer, the five-year survival rate for OSCC remained undesirable, and 35-55% patients developed recurrence within two years even with multimodality therapeutic strategies. Hence, identification of novel biomarkers for diagnosis and evaluating clinical outcome is of vital importance. MicroRNAs are 22-24 nt non-coding RNAs that could bind to 3′ UTR of target mRNAs, thereby inducing degradation of mRNA or inhibiting translation. Due to its implication in regulation of post-transcriptional processes, the role of miRNAs in malignancies has been extensively studied, among which the discovery of functional miR-9 in oral squamous cell carcinoma (OSCC) remained to be elucidated. We first demonstrated that miR-9 was down-regulated in 21 OSCC patients, and we further found that forced expression of miR-9 could result in deterred cell proliferation and decreased ability to migrate and form colonies. Flow cytometry displayed cell-cycle arrested at G0/G1 phase. We next used Targetscan to predict target genes of miR-9. CDK6, a protein highly implicated in cell cycle control, was chosen for verification. Down-regulation of CDK6 and Cyclin D1 in Tca8113 transfected with miR-9 mimics indicate that the complex formed by both proteins may be the effector of the antiproliferative function of miR-9 in OSCCs. Considering small molecules are developed to target CDK4/6, our finding may provide valuable scientific evidence for research and development of therapies and diagnostic methodology in OSCCs. [ABSTRACT FROM AUTHOR]