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关键词： GPCR   Signal crosstalk   Dimerisation   Effector   G protein   mAC   PLCβ   7TM   Seven-transmembrane   AKAP   A-kinase anchoring protein   BDNF   Brain-derived neurotrophic factor   BRET   Bioluminescence resonance energy transfer   Ca2   Calcium   CaM   Calmodulin   CaMKII   Calcium/calmodulin-dependent protein kinase II   CaMKIV   Calcium/calmodulin-dependent protein kinase IV   cAMP   Cyclic adenosine monophosphate   CTD   C-terminal domain   D1   Dopamine D1 receptor   D2   Dopamine D2 receptor   D5   Dopamine D5 receptor   DAG   Diacylglycerol   ER   Endoplasmic reticulum   EPSC   Excitatory postsynaptic current   FRET   Förster resonance energy transfer   FSK   Forskolin   GDP   Guanosine diphosphate   GEF   Guanine nucleotide exchange factor   GHSR   Growth hormone secretagogue receptor   GIRK   G protein-coupled inwardly rectifying potassium channel   GTP   Guanosine triphosphate   HD   Helical domain   HDX-MS   Hydrogen–deuterium exchange mass spectrometry   HTRF   Homogeneous time-resolved fluorescence   IP   Inositol 1,4,5-trisphosphate   membrane adenylyl cyclase   mGluR   Metabotropic glutamate receptor   MSN   Medium spiny neuron   PDE   Phosphodiesterase   PH   Pleckstrin homology   PI   Phosphoinositide   PIP   Phosphatidylinositol 4,5-bisphosphate   PKA   Protein kinase A   PKC   Protein kinase C   PLA   Proximity ligation assay   PLA₁/PLA   Phospholipase A1 / A2   Phospholipase C beta   PLD   Phospholipase D   RGS   Regulator of G protein signalling   RT-PCR   Reverse transcription polymerase chain reaction   TM   Transmembrane   TRPM5   Transient receptor potential melastatin 5  

摘要： G protein-coupled receptors (GPCRs) classically signal through cognate heterotrimeric G proteins to regulate second messengers such as cyclic adenosine monophosphate (cAMP) and intracellular Ca²⁺. Yet when two GPCRs are co-expressed, their combined activation can generate emergent outputs, including atypical Ca²⁺ mobilisation, non-linear cAMP responses, and cross-antagonism, that do not occur when either receptor is stimulated alone. Such phenotypes are often attributed to heteromerisation or higher-order receptor complexes. Here, we show that many of these behaviours can be parsimoniously explained by downstream effector integration which may not require obligate GPCR dimers. We focus on membrane adenylyl cyclases (mACs) and phospholipase Cβ (PLCβ) isoforms as multi-input integrators that decode convergent Gα_s/olf, Gα_i/o, Gα_q/11, Gβγ, Ca²⁺/calmodulin, and kinase signals according to isoform-specific regulatory logic and subcellular organisation. We also highlight how Gβγ dimers are not generic signalling by-products, but selective effectors whose actions depend on subunit composition, effector identity, and microdomain context. Using D₁–D₂, 5-HT₂A–mGlu₂, A₂A–D₂, and D₂–GHSR as case studies, we show how paradigmatic “heteromer” phenotypes can be reframed as effector-level coincidence detection and compartmentalised crosstalk, and we outline experimental strategies to distinguish receptor-receptor allostery from shared-effector integration.

关键词： Subperiosteal implant   CAD/CAM   Digital workflow   Atrophic maxilla   Peri-implantitis   Oral rehabilitation  

摘要： This case report describes the digital workflow and clinical outcomes of a customized CAD/CAM-assisted subperiosteal implant (SPI) used for the rehabilitation of a severely atrophic maxilla. A 53-year-old female patient presented with advanced peri-implantitis affecting multiple maxillary implants. After implant removal and a healing period, a patient-specific titanium SPI was designed and fabricated using cone-beam computed tomography and CAD/CAM technology. The implant was installed under conscious sedation, supporting a provisional prosthesis, followed by a definitive titanium–composite hybrid restoration. The digital workflow allowed precise adaptation of the implant to the patient’s anatomy, minimizing surgical morbidity and eliminating the need for bone grafting.. This case suggests that a customized CAD/CAM-assisted subperiosteal implant (SPI) may represent a feasible treatment alternative in a single-case salvage scenario, achieving favorable aesthetic and functional outcomes in a severely atrophic maxilla where rehabilitation with conventional endosseous implants is not feasible.

关键词： Antimicrobial film   CAM 21 bacteriophage   Phage stability   Film physiochemical and mechanical properties   Food safety and preservation  

摘要：

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  Carbohydrate-based films were developed as delivery matrices for novel phage CAM-21.
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  CAM-21 remained viable in all films for over 120 days at room temperature.
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  Confocal microscopy confirmed uniform phage distribution within film matrices.
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  Phage-incorporated films reduced E. coli O157:H7 on spinach and beef.
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  Pullulan-based films exhibited high opacity indicative of light barrier properties.

关键词： VNS   Remote maintenance   Shield plug   Design integration   CAD  

摘要： The Volumetric Neutron Source project, launched in 2023, primarily aims to test major in-vessel components within a new test facility based on the tokamak configuration. During the project's preliminary study phase, particular attention is also given to remote maintenance aspects, which are influencing and contributing to the definition of the in-vessel components design and the overall machine layout.

关键词： Colchicine   Inflammation   Atherosclerosis   Clinical trials   Mechanisms   AAA   abdominal aortic aneurysm   ACS   acute coronary syndrome   AF   atrial fibrillation   ALT   alanine aminotransferase   APC   antigen-presenting cell   AST   aspartate aminotransferase   BMS   bare-metal stent   CABG   coronary artery bypass grafting   CAD   coronary artery disease   CCS   chronic coronary syndromes   CK   creatine kinase   CLEAR   Colchicine and Spironolactone in Patients with Myocardial Infarction   COCOMO-ACS   Colchicine and Coronary Microvascular Obstruction in Acute Coronary Syndromes   COCS   COlchicine in Cardiac Surgery   COLIN   COLchicine in myocardial INfraction   COLCOT   Colchicine Cardiovascular Outcomes Trial   COP-AF   Colchicine for the Prevention of Perioperative Atrial Fibrillation   COPE   COlchicine for acute PEricarditis   COPPS   Colchicine for the Prevention of the Post-pericardiotomy Syndrome   COPS   COlchicine for Patients with acute coronary Syndrome   CORP   COlchicine for Recurrent Pericarditis   COVID-19   coronavirus disease 2019   CRP   C-reactive protein   CT   computed tomography   CYP3A4   cytochrome P450 3A4   ECG   electrocardiogram   eGFR   estimated glomerular filtration rate   ESC   European Society of Cardiology   FMF   Familial Mediterranean Fever   FOXO3A   forkhead box protein O3A   GDF15   growth differentiation factor 15   GTP   guanosine triphosphate   HFpEF   Heart Failure with Preserved Ejection Fraction   hs-CRP   high-sensitivity C-reactive protein   HUVECs   human umbilical vein endothelial cells   ICAM-1   intercellular adhesion molecule-1   ICAP   Investigation on Colchicine for Acute Pericarditis   IFN-γ   interferon-γ   IL-1β   interleukin-1β   IL-2   interleukin-2   IL-6   interleukin-6   IL-17 A   interleukin-17 A   IL-18   interleukin-18   IMPROVE-PVI   Impact of Short-Course Colchicine Versus Placebo After Pulmonary Vein Isolation   LOX-1   lectin-like oxidized LDL receptor-1   MAPK   mitogen-activated protein kinase   MI   myocardial infarction   MRI   magnetic resonance imaging   MYOCD   myocardin   NETs   neutrophil extracellular traps   NF-κB   nuclear factor kappa-light-chain-enhancer of activated B cells   NK   natural killer   NLRP3   NACHT   LRR   and PYD domains-co  

摘要： Colchicine, an ancient anti-inflammatory alkaloid, has been successfully repurposed as a cardiovascular therapeutic agent. This review synthesizes the evolving clinical evidence and mechanistic underpinnings of colchicine's action across a spectrum of cardiovascular diseases. Robust data from randomized trials support its efficacy in reducing recurrences of acute and recurrent pericarditis. In atherosclerotic coronary artery disease, long-term, low-dose colchicine has been shown to significantly reduce major adverse cardiovascular events in patients with chronic coronary syndromes, prompting its inclusion in international guidelines. However, not all trials have yielded consistent results; for instance, in the setting of recurrent myocardial infarction, some studies have failed to demonstrate significant benefit, highlighting issues of reproducibility and patient heterogeneity that have emerged across cardiovascular outcome trials. Evidence for its utility in other settings, such as preventing postoperative atrial fibrillation or ischemia-reperfusion injury, remains inconsistent, and a clear dose-response relationship has yet to be established. The therapeutic benefits are primarily attributed to the pleiotropic anti-inflammatory mechanisms, including microtubule disruption, inhibition of the NLRP3 inflammasome, and modulation of neutrophil and macrophage functions. Despite a narrow therapeutic index, low-dose regimens are generally well-tolerated, with gastrointestinal disturbances being the most common adverse effect. Its pharmacokinetics, notably metabolism via CYP3A4 and transport by P-glycoprotein, necessitate caution regarding drug interactions and use in renal/hepatic impairment. Future research should focus on precise patient stratification, combination therapies, and exploring its potential in emerging cardiovascular indications, solidifying its role in anti-inflammatory therapy.

关键词： BCAR1   CRK   Coronary artery disease   DOCK1   Indel variant   Sudden cardiac death  

摘要： Sudden cardiac death (SCD) is a leading cause of global mortality, with coronary artery disease (CAD) being the primary etiology. Vascular smooth muscle cell (VSMC) migration and proliferation, regulated by actin cytoskeletal dynamics, are pivotal to CAD pathogenesis. The integrin-focal adhesion-cytoskeleton signaling axis modulates these processes; however, its genetic contribution to SCD-CAD remains poorly understood. In this case-control study of a southern Chinese Han population (239 SCD-CAD cases; 594 healthy controls), we investigated 10 insertion-deletion (indel) polymorphisms across eight key genes within this axis. Using multiplex fluorescent PCR and capillary electrophoresis (CE), followed by logistic regression and haplotype analyses, we identified three protective variants: rs10599004 (OR = 0.78, p = 0.018), rs143263543 (OR = 0.70, p = 0.024), and rs58213835 (OR = 0.80, p = 0.046). Additionally, a significant risk haplotype was identified in BCAR1 (ins-rs149617239-ins-rs58213835, p = 0.007). Mendelian randomization (MR) analysis further supported the causal roles of genetically predicted BCAR1, CRK, and DOCK1 expression in cardiovascular risk. These findings underscore the involvement of this signaling axis in SCD-CAD susceptibility and suggest these genetic markers as potential tools for cardiovascular risk assessment as well as forensic molecular autopsy. Further validation through large-scale cohort studies and functional assays is essential to fully elucidate the underlying molecular mechanisms.

关键词： Amplitude-controllable technique   Cam excitation   Energy conversion   Multiple PZT vibrators   Piezoelectric transduction   Vibration energy harvesting  

摘要： Low-power electronics and wireless sensor networks require sustainable, maintenance-free power supplies. Piezoelectric vibration energy harvesters (PVEHs) are promising candidates, yet their performance is constrained by resonance dependence, narrow operating bandwidth, and robustness degradation from excessive structural deformation. Existing PVEHs still face difficulties in simultaneously achieving smooth amplitude limitation, stable low-frequency operation, and reduced tensile stress in PZT elements. To address these challenges, this study proposes a cam-driven energy harvester with multiple amplitude-controllable PZT vibrators (Mac-PVEH). The cam profile geometrically constrains the vibrator deformation and maintains the PZT elements mainly under unidirectional compressive loading. Finite element simulations and prototype experiments were conducted to evaluate its performance. Results show that the mechanism effectively suppresses excessive vibrator deflection, enhancing structural integrity under large amplitudes. The Mac-PVEH achieves wide low-frequency operation through proof mass and mass arm tuning. It delivers a peak power of 6 mW at 7.8 Hz under an optimal load of 60 kΩ and can power > 250 commercial LEDs. This work provides a cam-geometry-based design strategy for robust low-frequency PVEHs. In this strategy, cam lift regulates the maximum PZT deformation, lift angle controls access to the dwell-circle constraint, and proof mass and arm length tune the operating frequency range.

关键词： hepatic steatosis index   fibrosis-4 index   coronary heart disease   glucose metabolic states  

摘要： Nonalcoholic fatty liver disease frequently coexists with diabetes (DM and both are associated with an increased risk of coronary heart disease (CHD). The effect of nonalcoholic fatty liver disease progression or regression on the severity of coronary artery disease (CAD) in patients with CHD or DM remains unclear. In this multicenter study, 3126 patients with CHD, hepatic steatosis and fibrosis were assessed using the hepatic steatosis index (HSI) and fibrosis-4 index. CAD severity was evaluated using coronary angiography. After adjusting for confounders, hepatic steatosis (HSI > 36) was found to be associated with an increased risk of multivessel CAD. In patients with both hepatic steatosis and significant fibrosis (HSI > 36, fibrosis-4 index >= 1.3 the risk was further elevated (odds ratio [OR 1.596;95% confidence interval [CI 1.245-2.046 with a stronger association in patients with DM (OR: 1.988;95% CI: 1.041-3.835). Hepatic steatosis and/or significant fibrosis were associated with CAD severity, especially in individuals with both CHD and DM.

关键词： Denture base resins   Three-dimensional printing   Biofilm formation   Artificial aging   Physical properties  

摘要： Purpose: This study aimed to evaluate the performance of 3D-printed denture base resins (DBRs) compared with conventionally printed DBRs, examine their biofilm formation and physical properties, and determine the viability of 3D-printed DBRs as a superior alternative in removable prosthodontics. Methods: The DBR samples were fabricated using traditional packing (TRA milling (MIL and 3D printing (3DP) methods. All samples were serially polished with an abrasive paper. Biofilm formation was assessed using SYTO 9 and propidium iodide staining as well as confocal laser scanning microscopy. Color and dimensional stability were evaluated following immersion in artificial saliva, and volumetric changes were assessed after the samples were subjected to thermocycling (TC) and highly accelerated stress (HA) aging. Statistical analyses were conducted using one-way analysis of variance with post-hoc Tukey's honestly significant difference test (alpha = 0.05). Results: MIL exhibited the highest Aggregatibacter actinomycetemcomitans biofilm coverage (94.59% whereas 3DP exhibited the lowest coverage (58.86%). All DBRs exhibited slight perceptible color changes after immersion in artificial saliva, with 3DP demonstrating the least dimensional changes (2.86%). Following TC and HA aging, all DBRs experienced a volume increase, with TC inducing greater volumetric changes (2.8%-3.9%) than HA (0.8%-2.4%);however, the difference was not statistically significant (P < 0.05). Conclusions: The 3D-printed DBRs demonstrated superior resistance to biofilm formation, along with good color and dimensional stability. These properties indicate strong potential for enhanced hygiene maintenance, esthetics, and longterm clinical performance in denture applications.