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关键词： Aqueous media   Diphenyl phosphine oxide,1,3 dimethyl barbituric acid   Green chemistry and Amberlyst-15   MCRs  

摘要： An on-water three-component coupling reaction via concurrent formation of CP and CC bonds in a single synthetic step is reported here. This efficient and atom-economical approach provides a powerful strategy for the construction of 3-(phosphoryl)methylbarbituric acid derivatives. This transformation proceeds via the direct phosphorylation of aldehydes and alkylation of 1,3-dimethylbarbituric acid mediated by Amberlyst-15 in an aqueous medium. The developed condition was found to be general and suitable for several electron rich and poor aldehyde derivatives as the coupling partner.

关键词： EU AI Act   Article 50(1)   Transparency obligation   AI-human interaction   Direct interaction   Standardised disclosure   AI regulation   AI governance   Algorithmic transparency   Consumer protection  

摘要： This paper critically examines Article 50(1) of the EU Artificial Intelligence Act, which establishes an obligation for providers of AI systems intended for direct interaction with natural persons to develop and design their AI systems in such a way that the natural persons concerned are informed about the interaction with an AI system. Through a doctrinal and functional analysis, the study explores the scope, legal structure, and limitations of this provision. It highlights significant uncertainties surrounding the definitions of “direct interaction” and “obvious” use cases and critiques the asymmetric allocation of responsibility to providers while excluding deployers. The analysis reveals that the current framework insufficiently safeguards the rights of individuals, particularly vulnerable groups, due to narrow content requirements, lack of effective remedies, and exemptions for law enforcement and ostensibly “obvious” AI use. The paper argues that transparency, while normatively essential, risks becoming a symbolic rather than a functional safeguard under the current regulatory design. It advocates for the extension of obligations to deployers, greater standardisation of disclosure mechanisms, and a restrictive interpretation of exemptions, particularly in contexts involving children, persons with disabilities, or covert AI deployment. The findings suggest that without further legislative or interpretative measures, Article 50(1) of the European AI Act will remain a formalistic gesture rather than a substantive guarantee of trustworthy human-AI-interaction. As such, the paper calls on the European Commission to issue comprehensive implementation guidelines and to address the regulatory asymmetries that hinder the provision’s effectiveness in real-world contexts.

关键词： Cyclic adenosine monophosphate   Insulin resistance   Salt-inducible kinase 1   Skeletal muscle   Smad   Transforming growth factor β  

摘要： Excessive lipid accumulation in skeletal muscle contributes to insulin resistance. Salt-inducible kinase 1 (SIK1) is known to be involved in myogenic differentiation, yet its role in lipid-induced skeletal muscle insulin resistance remains unclear. Here, we identified the functional role of SIK1 in skeletal muscle insulin resistance under lipid overload and delineated the underlying signaling mechanisms. In C2C12 myotubes, palmitate markedly increased SIK1 expression and phosphorylation at Thr182, and further impaired insulin-stimulated Akt phosphorylation and glucose uptake. These effects were blocked by SIK1 knockdown or pharmacological inhibition of SIK. The palmitate-induced upregulation of SIK1 and the associated insulin signaling defects were abolished by inhibition of TGFβ receptor 1 or knockdown of Smad2/3. Moreover, genetic or pharmacological inhibition of SIK1 restored the palmitate-reduced cAMP levels in myotubes, and inhibition of PDE4 similarly rescued cAMP levels and insulin signaling, mimicking the effects of SIK1 suppression. Consistent with these in vitro findings, SIK1 and TGFβ1-Smad2/3 signaling were upregulated while cAMP levels were decreased in skeletal muscle of diet-induced obese (DIO) mice. Either SIK inhibition or blockade of TGFβ1-Smad2/3 signaling restored the impaired insulin-stimulated Akt phosphorylation in isolated skeletal muscle. Together, we demonstrate that SIK1 is upregulated under lipid overload via TGFβ1-Smad2/3 signaling, thereby triggering PDE4-dependent cAMP degradation and consequent insulin resistance in skeletal muscle. These findings establish SIK1 as a critical mediator of lipid overload-induced insulin signaling defects in skeletal muscle.

关键词： 诺卡菌   抗感染   药学监护   临床药师  

摘要： 诺卡菌是一种机会性致病菌,广泛分布于自然界中,可经皮肤破损处或呼吸道侵入人体,引起急性、亚急性或慢性感染性疾病。诺卡菌病预后较差,病死率高。其高危人群主要是长期应用激素或免疫抑制剂的人群,包括HIV感染、恶性肿瘤、器官移植、造血干细胞移植患者。近年来由于激素、免疫抑制剂的广泛使用,诺卡菌感染呈上升趋势。本文报道临床药师参与1例诺卡菌感染的治疗过程,探索临床药师开展药学服务,为临床药物治疗提供参考。

关键词： 慢性前列腺炎   氧化应激   白细胞介素-1   白细胞介素-1受体相关激酶   TLR-4/IRAK1/NF-κB p65通路   大火草  

摘要： 目的探讨氧化应激与白细胞介素-1(IL-1)交叉对话在自身免疫性前列腺炎(EAP)大鼠慢性炎症中的作用及大火草干预的可能机制。方法将30只Wistar大鼠随机分为5组,即正常组、模型组、大火草低、中、高剂量组,每组6只。药物干预后,采用WB法检测前列腺组织Toll样受体4(TLR-4)、IL-1受体相关激酶(IRAK1)、磷酸化核转录因子-κB p65(pNF-κB p65)蛋白,比色法检测血清谷胱甘肽过氧化物酶(GSH-PX)、超氧化物歧化酶(SOD)、丙二醛(MDA)水平,ELISA法检测炎症因子IL-1β、IL-10。结果模型组与正常组比较,大鼠前列腺TLR-4、IRAK1和pNF-κB p65蛋白表达显著升高(P<0.01);血清SOD、GSH-PX水平下降,MDA水平升高(P<0.01);血清IL-1β水平升高(P<0.01)。与模型组比较,大火草可以显著下调EAP大鼠前列腺组织TLR-4、IRAK1、pNF-κB p65蛋白表达(P<0.01);可以提高血清SOD、GSH-PX水平,降低血清MDA水平(P<0.01或P<0.05);还可以显著降低血清IL-1β水平,提高IL-10水平(P<0.01或P<0.05)。大火草可以减轻前列腺腺体损伤和炎症细胞浸润。结论IRAK1可能是EAP大鼠局部炎症过程中氧化应激与IL-1β交叉对话的关键节点。大火草可能通过调节TLR-4、IRAK1、pNF-κB p65表达,减轻氧化应激和IL-1β的水平,改善前列腺慢性炎症。

关键词： Dark Matter at Colliders   Models for Dark Matter   Neutrino Mixing   Particle Nature of Dark Matter  

摘要： We study a U (1)B−L extension of the Standard Model (SM) in which Dirac neutrino masses are generated radiatively at the one-loop level through the exchange of new beyond the SM fields. This framework establishes a direct connection between neutrino mass generation and the dark sector, with the stability of the dark matter ensured by a residual discrete Z6 symmetry arising from the spontaneous breaking of U (1)B−L. We investigate the resulting charged lepton flavor violating processes and dark matter phenomenology, saturating relic observations and direct-detection constraints, and analyze the collider signatures of the dark sector at the Large Hadron Collider, its proposed high luminosity extension and at a future muon collider. We have identified excellent prospects for observing the considered dark matter candidates in these colliders, even with lower integrated luminosities than the proposed one.

关键词： Monomer   Polymeric materials   Condensation polymerization   Microstructure  

摘要： Aromatic polyamides are an important class of high-performance polymers; however, achieving a balance between rigidity, processability, and tunable physicochemical properties remains a challenge. In this study, two structurally related aromatic polyamides (PAM and PAM-2) were synthesized via Yamazaki-Higashi phosphorylation polycondensation using a bisphenol-A-based diacetic acid monomer and two different diamines, namely 2,6-diaminopyridine and 1,4-phenylenediamine. The synthesized polymers were comprehensively characterized by FTIR, ¹H NMR, XRD, FESEM-EDAX, elemental mapping, GPC, inherent viscosity, contact angle measurements, tensile testing, and thermal analysis (TGA/DTG). The results confirmed successful polymer formation with moderate molecular weight and narrow distribution. Both polymers exhibited amorphous nature and good solubility in polar aprotic solvents. Comparative analysis revealed that the incorporation of pyridine units in PAM enhances intermolecular interactions, leading to improved tensile strength (∼38 MPa), good thermal stability, and enhanced char residue (∼40% at 800 °C). In contrast, PAM-2 showed comparatively lower mechanical and thermal performance but exhibited more compact morphology and reduced surface wettability (contact angle ∼90°). These findings demonstrate that subtle variations in diamine structure significantly influence the structure-property relationship of aromatic polyamides. This work provides useful insights into the rational design of polyamide materials with tunable properties, while potential applications are suggested cautiously and require further investigation.

关键词： Type 1 diabetes (T1D)   Children and adolescents   HbA1c   Parental diabetes burden   Relationship satisfaction  

摘要： To examine relationship quality in parents of children with type 1 diabetes (T1D) and its associations with parental and child outcomes.