Rui Zhou

Iron (Fe), copper (Cu), and zinc (Zn) are essential trace elements for cardiovascular and cerebrovascular homeostasis, acting as enzymatic cofactors in energy metabolism and antioxidant defence. However, disruption of metal homeostasis can amplify oxidative injury through direct Fe/Cu redox chemistry or indirect Zn-dependent pathways. Ferroptosis and cuproptosis have been investigated as context-dependent mechanisms in various cardiovascular and cerebrovascular diseases (CCVDs), such as atherosclerosis, ischaemic/haemorrhagic stroke, diabetic vascular disease, and abdominal aortic aneurysm. This review summarizes the physiological regulation of metal homeostasis and examines pathways through which metal dyshomeostasis may contribute to vascular and neural injury, including oxidative biomolecular modification, mitochondrial dysfunction and inflammatory signalling. It further summarizes therapeutic strategies targeting metal metabolism, such as metal chelators, trace element supplementation and nanomedicine-based targeted delivery systems, which have shown protective effects predominantly in experimental models by restoring metal homeostasis and scavenging reactive oxygen species. Finally, the review highlights key challenges in clinical translation, such as tissue-specific metal detection and targeted inhibitor development, and emphasizes that precise regulation of metal metabolism may offer therapeutic opportunities for CCVDs.

Transdermal microneedles (MNs) offer a minimally invasive and highly compliant approach for delivering macromolecular therapeutics. However, the clinical translation of conventional conical and pyramidal MNs is hindered by an intrinsic mechanical trade-off: minimizing tip diameter reduces insertion force but increases fracture susceptibility, whereas enlarging the base improves structural robustness at the cost of higher skin insertion resistance. Furthermore, closely spaced MN arrays frequently suffer from the "bed-of-nails" effect, which precludes adequate tissue penetration. Inspired by the open-groove fangs of opisthoglyphous snakes, which evolved for low-resistance tissue puncture, we designed and systematically optimized snake fang-inspired microneedles (SF-MNs). Using a three-layer hyperelastic Neo-Hookean skin model, we conducted finite element analyses on 27 distinct SF-MN configurations to evaluate their static strength and dynamic insertion mechanics. The optimal SF-MN structure (500 [Formula: see text] length, 30 [Formula: see text] groove depth, 10 [Formula: see text] tip diameter) demonstrated superior lateral structural stability (safety factor > 0.6) and achieved significantly lower insertion forces compared to size-matched conical MNs. Notably, SF-MN arrays mitigated the "bed-of-nails" effect, narrowing the critical inter-needle spacing triggering range to 396-402 [Formula: see text]-markedly lower than the 440-700 [Formula: see text] range of conventional arrays. By leveraging groove-induced tissue diversion and contact area reduction, these biomimetic arrays enable deeper skin penetration, offering a robust and highly efficient platform for transdermal drug delivery in chronic disease management.

The prevention and treatment of cardiovascular disease (CVD) are undergoing a paradigm shift from a lipid-centric approach to a holistic metabolic perspective. Central to this evolution is the gut–fat–heart axis, a sophisticated three-dimensional communication network that integrates neural, endocrine, and immunometabolic signaling to regulate systemic lipid homeostasis. This manuscript systematically explores how the gut microbiota acts as a “metabolic organ” to remotely control host health through the production of bioactive metabolites and the modulation of molecular communication networks. At the physiological level, microbial products such as short-chain fatty acids (SCFAs) and modified bile acids regulate energy balance and lipid synthesis via the FXR-FGF15/19 axis and G protein-coupled receptors. Furthermore, gut hormones like GLP-1 and neuro-reflex pathways involving the vagus nerve provide rapid control over postprandial lipid clearance and feeding behavior. Conversely, pathological dysbiosis triggers the accumulation of harmful metabolites, such as trimethylamine N-oxide (TMAO) and lipopolysaccharides (LPS), which drive lipotoxicity, vascular inflammation, and “dysfunctional HDL” formation. These processes accelerate the progression of atherosclerosis, heart failure, and metabolic syndrome. Finally, the article outlines promising clinical translation strategies, including the development of TMA lyase inhibitors, next-generation probiotics, and the use of phytochemicals to reshape the microbial landscape. By decoding the molecular dialogues within the gut–fat–heart axis, this research provides a novel strategic vantage point for the integrated management of cardiovascular–kidney–metabolic (CKM) syndrome.

The mammalian brain fundamentally relies on precise lipid homeostasis to maintain structural integrity and complex neural signaling. Emerging evidence positions lipid metabolism reprogramming not merely as a secondary pathological byproduct but as a core initiating driver of age-related neurodegenerative diseases. This review systematically evaluates the mechanisms of cerebral lipid dyshomeostasis during brain aging, highlighting glial cells as the central mediators of this pathological cascade. We comprehensively dissect the age-associated “lipid drift”, emphasizing apolipoprotein E (APOE)-induced cholesterol transport defects and lipid raft pathology, the accumulation of lipid droplets that triggers microglial metabolic stress (LDAMs), and ceramide-driven neuronal apoptosis coupled with the exosome-mediated propagation of pathogenic proteins. Furthermore, we map these aberrant lipid networks to specific pathological signatures in Alzheimer’s, Parkinson’s, and demyelinating diseases. Finally, we critically evaluate promising therapeutic interventions, including nutritional strategies, LXR/RXR agonists, and nanotechnology-enabled delivery systems designed to bypass the blood–brain barrier. By integrating high-throughput lipidomics for early diagnostic biomarker discovery, we underscore the translational imperative of restoring cerebral lipid homeostasis as a disease-modifying strategy for neurodegeneration.

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, and residual inflammatory risk persists despite optimal lipid and glucose control. Emerging evidence indicates that metabolic reprogramming within immune cells constitutes a central driver of cardiovascular immune injury. In this review, we propose a unifying framework in which glyco-lipotoxicity acts as a primary metabolic trigger, inducing mitochondrial dysfunction, oxidative stress, and activation of the NLRP3 inflammasome and cGAS–STING pathways. Hyperglycaemia and dyslipidaemia reshape intracellular metabolic circuits, enhancing glycolysis and disrupting oxidative phosphorylation, thereby promoting sustained pro-inflammatory phenotypes. Crucially, metabolic intermediates function as cofactors for epigenetic remodelling. This establishes trained immunity in both circulating innate immune cells and haematopoietic stem/progenitor cells, which serves as the cellular basis for persistent metabolic memory. This persistent immunometabolic imprint amplifies sterile inflammation and accelerates vascular and myocardial remodelling. Furthermore, these processes are systemically propagated through cross-organ communication networks, including the heart–adipose, gut–heart, and cardio-hematopoietic axes, forming a multidimensional inflammatory amplification loop. We also summarise emerging therapeutic strategies targeting the metabolic–epigenetic axis, aiming to reverse maladaptive trained immunity and mitigate residual CVD risk. By integrating immunometabolism, epigenetic regulation, and organ crosstalk, this review highlights metabolic reprogramming as a pivotal mechanistic nexus and potential precision target for cardiovascular protection.

The clearance efficiency of allergen particles during nasal irrigation is a quantitative standard for evaluating the effectiveness of nasal irrigation. Due to the difficulty in obtaining various parameters in in vivo experiments, this study aims to establish a numerical model of the nasal cavity based on CT scan images of healthy adults. We chose four different levels of allergen particles, PM1, PM5, PM10, and PM25, as the subjects. A quantitative analysis was conducted to determine the clearance efficiency of the four levels of allergen particles by five different inlet flow rates of the irrigation solution. The results showed that the clearance efficiency of PM1 allergens was optimal at the inlet flow rate of 1.8 [Formula: see text], equivalent to 2.10 [Formula: see text]. In summary, selecting an appropriate flow rate is necessary to achieve the best clearance efficiency for different levels of allergen particles.

Paeoniflorin is a natural pharmaceutical ingredient with a widely biological activity. However, as a hydrophilic drug, the problem of low transdermal rate limits its clinical application. To overcome this shortage, LUVs were used as biocompatible carriers of paeoniflorin in this study. We prepared paeoniflorin-loaded large unilamellar vesicles (LUVs) with W/O/W structure by microfluidics. We used four kinds of chips to prepare paeoniflorin LUVs and explored the effects of the chip structures on LUVs properties applying both experiments and numerical simulations. The difference of fluid mixing mechanisms was analyzed among four different channels, including straight and curved structures. Then we evaluated the differences in skin permeability among the three groups, paeoniflorin aqueous solution group, drug-loaded liposome group and blank liposome & drug mixture group, using the abdominal skin of male mice. The results showed that the structure of the microfluidic channel was a key factor affecting the flow rate and mixing efficiency. The mixing efficiency further affected the liposome size. The mixing efficiency of curved channel was not better than that of a straight channel due to the low flow rate and long mixing time. By the results of transdermal experiments, LUVs could reduce the transdermal time and increase the total transdermal amount. LUVs effectively improved the transdermal absorption efficiency of paeoniflorin. In conclusion, paeoniflorin LUVs with highly efficient transdermal were successfully prepared by using microfluidics. We explored the underlying fluid dynamics that lead to variations in the preparation with different chip structures. The transdermal effect of the LUVs was verified. Graphical Abstract

The main advantages of microneedles are precise drug delivery through human skin, minimal tissue damage and painlessness. We conducted structural analysis and skin puncture studies of hollow microneedles using ANSYS for three materials: Hafnium Dioxide (HfO₂), Polyglycolic acid (PGA) and Polylactic acid (PLA). Firstly, we selected three lengths, three tip diameters and three base diameters to conduct a L₉(3⁴) orthogonal experiment. Thus, we obtained nine different single-needle structures for each material, totaling 27 models for three materials. Subsequently, we investigated the stability and puncture properties of single needles. The optimal structures of the single-needle for three materials were same. Then, we used the optimal structure of the single-needle to establish the double-needle, triple-needle and five-needle models with ten different spacings. The simulations were carried out to examine the maximum stress during puncture. Finally, we investigated the hydrodynamic properties of water and lidocaine ibuprofen [Lid][Ibp] in the lumen of the microneedle. The results indicated that the optimal spacing of multi-needles varies depending on the material. The flow velocity of the fluid in the lumen is positively correlated with the pressure. Increasing the pressure can effectively reduce the flow velocity loss of low-viscosity fluid.

Background/Objectives: Numerical simulation plays an important role in pharmaceutical preparation recently. Mechanistic models, as a type of numerical model, are widely used in the study of pharmaceutical preparations. Mechanistic models are based on a priori knowledge, i.e., laws of physics, chemistry, and biology. However, due to interdisciplinary reasons, pharmacy researchers have greater difficulties in using computer models. Methods: In this paper, we highlight the application scenarios and examples of mechanistic modelling in pharmacy research and provide a reference for drug researchers to get started. Results: By establishing a suitable model and inputting preparation parameters, researchers can analyze the drug preparation process. Therefore, mechanistic models are effective tools to optimize the preparation parameters and predict potential quality problems of the product. With product quality parameters as the ultimate goal, the experiment design is optimized by mechanistic models. This process emphasizes the concept of quality by design. Conclusions: The use of numerical simulation saves experimental cost and time, and speeds up the experimental process. In pharmacy experiments, part of the physical information and the change processes are difficult to obtain, such as the mechanical phenomena during tablet compression and the airflow details in the nasal cavity. Therefore, it is necessary to predict the information and guide the formulation with the help of mechanistic models.