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关键词： Waist circumference   VAT   Body weight   BMI   Age   Meta-analysis  

摘要： Central obesity, commonly assessed using waist circumference (WC), is strongly associated with cardiometabolic risk. While lifestyle interventions and glucagon-like peptide-1 receptor agonist-based therapies (GLP-1RA-based therapies) reduce body weight, their effects on WC and factors influencing response remain incompletely characterised. This systematic review and meta-analysis evaluated the effects of these interventions on WC in randomised controlled trials (RCTs).

摘要： We generated and validated a vascular Ehlers-Danlos syndrome (vEDS) human iPSC line, JHUi009-A, carrying a pathogenic COL3A1 c.2456G > A variant, and a CRISPR/Cas9-edited isogenic control line, JHUi009-A-1. Reprogramming was performed on expanded erythroid progenitor cells using an integration-free Sendai virus system. Both lines showed typical pluripotent colony morphology, expressed stemness-associated transcription factors, retained a normal 46, XY karyotype, and differentiated into derivatives of all three germ layers. These hiPSC lines differentiated into vSMCs, with mutant vSMCs showing higher contractile marker expression than the corrected control, supporting their use as an in vitro model of a COL3A1-associated vascular phenotype.

关键词： DNA damage response   Autophagy   Cancer   Cellular stress and MDC1  

摘要： Cancer cells undergo various adaptive measures to survive the high level of oxidative stress that threatens genomic integrity and survival. This oxidative stress is enhanced during cancer chemotherapy and undermines the drug efficacy due to the altered cellular signalling, which promotes cell survival and cancer progression. While oxidative stress induces autophagy, the ensuing genotoxic stress activates the DNA damage response (DDR) in cancer cells. Cancer cells show high dependency on these mechanisms for survival, which also indicates the likelihood of increased cooperativity between them under stress. In this study, through co-immunoprecipitation and immunofluorescence assays, we have demonstrated strong interaction between MDC1 and Beclin-1 in H₂O₂ and doxorubicin treated HeLa cells. Furthermore, we observed that in Hela cells depleted of MDC1, the translocation of Beclin-1 to the nucleus was abrogated, which adversely affected both the DDR and autophagy response in these cells. Additionally, we have analyzed the effect of CHK2 kinase activity on this interaction, and the presence of phospho-CHK2 probably supports the nuclear activity of Beclin-1 through its phosphorylation, but is dispensable for the nuclear translocation of Beclin-1. In conclusion, our findings contribute to the understanding of the crosstalk between DDR and autophagy for cell survival under genotoxic stress, with potential implications on the efficacy of drug treatment.

摘要： Rice blast, caused by Magnaporthe oryzae, remains difficult to manage because race-specific R genes are rapidly overcome. Pi21 is an atypical blast susceptibility gene that encodes a proline-rich protein with a putative metal-binding and protein–protein interaction region, and loss-of-function alleles confer durable, non–race-specific resistance. Here, we first sequenced Pi21 from eight rice cultivars with contrasting blast responses and found none of the known 21- or 48-bp resistant haplotypes, supporting de novo editing of Pi21 in an indica background. We designed five CRISPR/Cas9 constructs targeting exon 1 and exon 2 of Pi21 and transformed the indica cultivar Kasalath. All targets produced edits, and T1 plants segregated to yield homozygous, Cas9-free lines carrying either early frameshifts or an in-frame 30-bp deletion within the proline-rich region. Detached-leaf assays with three M. oryzae isolates showed that frameshift alleles causing premature stop codons at amino acid 25 or 180 consistently reduced lesion length and lesion area, whereas the in-frame deletion conferred intermediate resistance. Edited lines with stronger resistance also showed higher induction of SA- and JA/ethylene-responsive defense genes such as PR1b, WRKY45 and PAL 48 h after inoculation, indicating that Pi21 normally suppresses multiple immune pathways. Agronomic evaluation of eight yield-related traits revealed that most edited lines were comparable to wild-type Kasalath. Together these data support a domain-level relationship between Pi21 disruption and enhanced resistant phenotype in indica rice and demonstrate that precise disruption of this susceptibility gene can deliver broad blast resistance without major yield penalties.

关键词： SrxBa1-xNb2O6   Piezoelectrics   Thin film   Chemical solution deposition   Orientation  

摘要： Tetragonal tungsten bronzes are normally uniaxial ferroelectrics making crystallographic texture pivotal for optimization of electrical properties. Sr_xBa_1-xNb₂O₆ (SBN), x = 0.4, 0.5 and 0.6, thin films with out-of-plane (001) or in-plane (310) oriented polarization were deposited by aqueous chemical solution deposition on SrTiO₃ (STO)(100) substrates. A texture degree of > 90% was achieved for (001) oriented SBN films on SrO terminated STO, while the (310) oriented films on TiO₂ terminated STO possessed a degree of texture > 50%. The films were in compression compared to bulk due to epitaxial strain, thermal strain, and a reduced lattice parameter of the film due to Ti-doping, all related to the substrate used. The Curie temperature of selected (001) oriented films showed the expected decrease with increasing Sr content, and additional decrease attributed to Ti-doping. A piezo response was measured in (001) oriented films by in situ application of an electrical field during X-ray diffraction measurements.

关键词： Endocannabinoid receptors   Social stress   Social reward motivation   Social interaction   Adolescence   Social operant conditioning  

摘要：

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  AM251 mitigated SS-induced reductions in social behaviour in female rats
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  No effect of SS or AM251 on corticolimbic protein expression in reward systems
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  Aberrant CB1R signaling may underlie the social deficits in SS female rats

关键词： 变应性鼻炎   小青龙汤   玉屏风散   肿瘤坏死因子-α   白细胞介素-lβ  

摘要： 目的基于核因子κB(nuclear factorκ-light-chain-enhancer of activated B cells,NF-κB)信号通路,观察小青龙汤、麻辛附汤合玉屏风散对变应性鼻炎(allergic rhinitis,AR)大鼠血清中肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)和白细胞介素-1β(interleukin-1β,IL-1β)含量的影响,探讨该复方治疗AR的作用机制。方法选取90只清洁级健康雄性Wistar大鼠(体质量200~240 g),购自辽宁中医药大学实验动物中心。采用随机区组法按体质量将大鼠分为9组(每组10只):空白对照组、AR模型对照组、吡咯烷二硫代氨基甲酸铵(pyrrolidine dithiocarbamate ammonium,PDTC)干预组、佛司可林(Forskolin)干预组、N-[2-(对溴肉桂酰氨基)乙基]-5-异喹啉磺酰胺二盐酸盐{H89 dihydrochloride[N-(2-p-Bromocinnamylamino ethyl)-5-isoquinolinesulfonamide dihydrochloride],H89}干预组、氯雷他定治疗组,以及小青龙汤、麻辛附汤合玉屏风散低、中、高剂量组。采用卵蛋白全身致敏联合局部攻击的方法制备AR模型,检测各组大鼠鼻黏膜中TNF-α和IL-1β含量。实验数据采用IBM SPSS Statistics 26软件进行单因素方差分析(One-Way ANOVA)。结果AR模型对照组血清中TNF-α和IL-1β含量显著升高。与AR模型对照组相比,Forskolin干预组、PDTC干预组及小青龙汤、麻辛附汤合玉屏风散各剂量组均能显著降低TNF-α和IL-1β含量(P<0.05);而H89干预组则显著升高上述炎症因子含量(P<0.05)。与小青龙汤、麻辛附汤合玉屏风散低剂量组相比,中、高剂量组对TNF-α和IL-1β的降低作用更显著,差异具有统计学意义(P<0.05)。结论小青龙汤、麻辛附汤合玉屏风散可能通过抑制NF-κB信号通路、激活环磷酸腺苷-蛋白激酶A信号通路,降低鼻黏膜TNF-α和IL-1β含量,从而发挥治疗AR的作用。其疗效呈现剂量依赖性,小青龙汤、麻辛附汤合玉屏风散中、高剂量组效果优于低剂量组,体现了中医治疗的量效关系。

关键词： Collision-induced absorption   Carbon dioxide   H2   Atmospheric composition   Binary absorption coefficients  

摘要： The collision-induced absorption (CIA) of a H${}_2$-CO${}_2$ mixture has been studied in the [3907, 4770] cm⁻¹ spectral range for temperatures ranging from 241 to 498 K. The experiments were based on the use of a new high-resolution Fourier spectrometer coupled with an atmospheric simulation chamber. Binary absorption coefficients (BACs) were measured for the first time in the [4033, 4730] cm⁻¹ spectral range at temperatures other than room temperature and are provided in tabular form. At room temperature, the results are compared with existing experimental data and theoretical coefficients, while for the other temperatures, only theoretical values are available. For all considered temperatures, we computed the theoretical integrated band intensity for the experimental BACs and the semi-empirical models. The calculations have been made over the reduced [4033, 4730] cm⁻¹ spectral range, and the entire band, in order to explore the bias induced by using a restricted spectral region. Furthermore, the H${}_2$

关键词： Continuous manufacturing   Twin-screw wet granulation   ConsiGma-1   Pharma-11  

摘要：

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  Granulation in Pharma-11effectively replicates CG-1 performance in continuous TSWG.
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  Formulation, L/S ratio and screw configuration influence granule properties.
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  Distributive mixing elements in screw configuration enhance particle coalescence.
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  Milling minimized scale effects, yielding uniform granules and tablet quality.