Jiang Xi Institute for Drug Control

Helicobacter pylori (H. pylori) infection has emerged as a serious risk factor for global human health. Current antibiotic-based clinical eradication therapies still have many challenges, including inadequate drug permeability across the gastric mucus barrier, H. pylori biofilm-induced antibiotic resistance and recurrent infections, as well as gut dysbacteriosis. Herein, we report a probiotic-nanozyme hybrid system (LP@FeTA/CuPt), which is formed by coupling polyphenol-coated Lactobacillus plantarum (LP@FeTA) and CuPt nanozymes. LP@FeTA effectively penetrates the gastric mucus barrier via autokinetic movement, and facilitates the targeted delivery of CuPt nanozymes within H. pylori biofilms by "eating" extracellular polymeric substances (EPS). CuPt nanozymes respond to the acidic and H2O2-rich biofilm microenvironment to generate reactive oxygen species (ROS) and release Cu ions, thereby achieving multi-target eradication of biofilms by interfering with H. pylori flagellar self-assembly, urease activity, outer membrane function and energy metabolism. Importantly, LP@FeTA/CuPt can be degraded by transferrin at the infection site, allowing the released CuPt nanozymes to reactivate the antibacterial immune functions of macrophage, thus eliminating biofilm-escaped bacterioplankton to prevent recurrent infections. Notably, LP@FeTA/CuPt also modulates gut microbiota homeostasis. This study provides a promising non-antibiotic therapeutic strategy for H. pylori infection.

BackgroundMetabolic dysfunction-associated fatty liver disease (MAFLD), characterized by abnormal accumulation of triglycerides (TG) and cholesterol in hepatocytes, is a globally prevalent chronic liver disease with a rising incidence that poses a severe threat to human health. In the absence of effective targeted drugs and long-term prognostic interventions for MAFLD, aerobic exercise, as a safe and accessible non-pharmacological strategy, is widely recognized to slow MAFLD progression. However, a systematic summary of its mechanisms in ameliorating MAFLD remains insufficient.Main bodyThis review integrates recent high-quality PubMed studies and classic models (e.g., high-fat diet-induced C57BL/6J mice, HepG2 cells) to analyze aerobic exercise’s therapeutic effects on MAFLD and underlying molecular mechanisms. Aerobic exercise regulates MAFLD via a multi-dimensional network. SESN family signaling regulates hepatic lipid metabolism, improves insulin resistance, enhances antioxidant capacity, and promotes lipophagy. miRNA-mediated regulation modulates lipogenic gene expression, insulin signaling, and fatty acid oxidation via exercise-induced changes in key miRNAs and their upstream regulators or downstream targets. AMPK-centered energy metabolism orchestrates fatty acid β-oxidation promotion and de-novo lipogenesis suppression through its related pathways. Other key pathways include inhibiting lipogenesis via exercise-induced IL-6, blocking hepatic inflammation through brown adipose-derived Nrg4, optimizing lipid droplet-mitochondria interaction by regulating PLIN5 and Mfn-2, and suppressing ferroptosis via activating antioxidant pathways. Notably, mechanisms initially validated in non-alcoholic fatty liver disease (NAFLD) are equally applicable to MAFLD, as both are characterized by core metabolic dysfunction.ConclusionAerobic exercise alleviates MAFLD progression by orchestrating a complex regulatory network involving energy metabolism, stress response, post-transcriptional modification, and inter-organ crosstalk. This review clarifies the key molecular targets and signaling pathways underlying aerobic exercise’s therapeutic effects, providing a theoretical basis for exploring potential targeted interventions and guiding future drug development for MAFLD.

Programmed cell death (PCD), a regulated cell death (RCD) subtype essential for physiological homeostasis, encompasses distinct mechanisms including apoptosis, necroptosis, autophagy, ferroptosis, cuproptosis, and pyroptosis. This evolutionarily conserved process critically regulates disease pathogenesis across degenerative disorders, malignancies, fungal infections, and vascular calcification (VC). VC manifests as pathological calcium deposition in cardiovascular tissues, impairing vascular elasticity and hemodynamics. These structural alterations elevate risks of atherosclerotic events, cerebrovascular accidents, and peripheral vascular dysfunction, while concomitantly inducing vital organ hypoperfusion and cardiac overload that predispose individuals to myocardial ischemia, left ventricular hypertrophy, and heart failure. Despite advances in delineating associated signaling networks, the molecular etiology of VC remains elusive, and effective therapeutic interventions are currently lacking. While systematically examining the pathophysiological contributions of both established and novel PCD mechanisms to VC progression, this review incorporates a discussion of cuproptosis as a novel form of PCD, which may serve as a target for atherosclerosis treatment. The inclusion of cuproptosis, alongside other PCD modalities, allows for a more integrated and updated perspective on the complex regulatory networks governing VC. Our objective is to synthesize the current understanding of how these diverse PCD pathways, both classical and emerging, collectively contribute to the disease pathogenesis and to explore the broader therapeutic potential of targeting PCD in VC.

为保护消费者健康，电子烟油中禁止添加咖啡因和牛磺酸。然而，由于这两个化合物极性差异大，针对它们的同时检测仍面临挑战。本研究通过筛选和优化不同功能团的色谱柱及其分离条件，使用同时具有多种分离模式的色谱柱，建立了高效液相色谱-串联质谱同时检测电子烟油中咖啡因和牛磺酸的分析方法。样品经50%乙腈水溶液提取，以乙腈和0.1%甲酸水溶液（含10 mmol/L甲酸铵）作为流动相梯度洗脱，使用FMD Comixsil ACRP色谱柱（100 mm×2.1 mm，3.0 µm）分离，在多反应监测模式下，通过串联质谱检测器进行检测，外标法定量。结果表明，咖啡因和牛磺酸在色谱柱上都得到了很好的保留，且峰形好，无拖尾。咖啡因在1.00~100 μg/L范围内线性关系良好（r=0.997），牛磺酸在10.0~1 000 μg/L范围内线性关系良好（r=0.998）。咖啡因、牛磺酸的检出限分别为0.100、1.00 mg/kg，定量限分别为0.250、2.50 mg/kg。在1倍、2倍、10倍3个添加水平下，各组分回收率为88.2%~99.0%，相对标准偏差（RSD）为2.2%~6.6%（n=6）。本方法简单、快速，灵敏度高，可为电子烟的质量监管提供技术支撑。

Viticis fructus (VF) is a valuable traditional Chinese herbal medicine with high commercial value. In the Chinese Pharmacopoeia (Ch.P., 2020 edition), the quality of VF is mainly evaluated by its casticin content. However, varying growth and production conditions, such as cultivation environment, origin, and harvesting process, result in highly variable yields, quality, and composition. The aim of this study was to propose a new method for discriminating and quantifying VF from different regions. The chemical constituents of VF from different regions were collected by ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) using electrospray ionization (ESI) in both positive and negative ion modes, and the chemical constituents were qualitatively analyzed by Waters UNIFI portal 1.9.4.0 software combined with the self-developed database of VF. The spectra obtained by Progenesis QI 27.26.1020 and EZinfo 2.0 software were processed by peak standardization, peak extraction, peak alignment, peak matching, and so forth, and the information of compound retention time and mass-charge ratio was obtained. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed by SIMCA-P 14.0 software to study the different components of VF from different regions. A total of 102 components were identified from VF. The results of PCA and OPLS-DA showed that there were significant differences in the chemical components of VF from different regions. Twenty-seven different components were obtained by variable importance for the projection (VIP) > 1 screening, including 12 terpenoids, 7 phenylpropyl compounds, 3 phenolic acids, 2 flavonoids, 2 fatty acids, and 1 steroid. By establishing a method of UPLC-QTOF-MS combined with multivariate statistical analyses, this study clarifies the difference in chemical components between VF from different regions, which provides a basis for the quality control of VF and provides basic information for revealing the impact of the ecological environment on the accumulation of compounds in VF.

The rapid advancements in autonomous driving technology necessitate the extensive deployment of automotive radars operating within the 77-81 GHz millimeter-wave band in the forthcoming years. In contrast to earlier Frequency Modulated Continuous Wave (FMCW) radars, Phase-Modulated Continuous Wave (PMCW) radars exhibit notable improvements in processing speed and flexibility, offering superior range and velocity resolution. These enhancements are critical for the precise detection and interpretation of dynamic and complex traffic scenarios. This paper initially presents the simulation and testing of algorithms for range and speed measurement using single-input single-output (SISO) PMCW millimeterwave radar. Building upon these results, further simulations incorporating multi-input multi-output (MIMO) systems utilizing Hadamard codes are conducted to augment PMCW radar performance. The final phase of this study involves implementing the relevant signal processing algorithms on a custom-developed digital signal processor (DSP) named SWIFT. Experimental findings demonstrate that PMCW radar significantly mitigates multipath effects and clutter, maintaining high performance in complex environments. Furthermore, the algorithms executed on the DSP meet the anticipated performance standards. The proposed methodology not only validates the theoretical framework but also establishes a foundation for future hardware implementation.

Abstract The development of new materials is of great significance for scientific and technological innovation and is essential in addressing significant societal challenges (1). Combinatorial material deposition techniques facilitate the understanding of composition-structure-property relationships and permit the rapid screening of materials across diverse compositional ranges (2). However, there are considerable challenges associated with the universal integration of multiple materials and the creation of gradient material libraries due to the lack of efficient mixing mechanisms and the difficulty in achieving precise and rapid dispensing (3-5). In this study, we introduce a novel printing approach for multicomponent gradient materials, which amalgamates various constituent materials for the three-dimensional printing of multiscale and high-throughput multigradient materials. This innovation overcomes the limitations of prolonged cycle times, high experimental costs, and low efficiency inherent in traditional manufacturing methods. First, we developed 3D-printed precursor materials that can be shaped arbitrarily. By meticulously proportioning the components of these precursor materials through high-throughput techniques and material libraries, we enable multi-degree-of-freedom adjustments in ratios and on-demand combinations, resulting in the fabrication of complex materials not achievable through conventional manufacturing processes. Subsequently, we established a highly adaptable self-propagating energy deposition technology based on the precursor materials, which reduces the conventional reliance on specific equipment and processes. Finally, we demonstrated the application of this technology through a printing strategy for various copper-based composites and multicomponent gradient materials, which allows for the simultaneous incorporation of an array of metallic and non-metallic compounds with graded properties across multiple compositions and structures. This advancement significantly enhances the scope of additive manufacturing applications in composition optimization, functional grading, and structural tuning, surpassing the capabilities of traditional printing methods. Our ability to synchronize the printing of multilayer gradient materials during the process, while mitigating thermal accumulation and structural defects such as cracks through thermal stacking between gradients, represents a marked improvement over traditional hot-cold stacking methods. Furthermore, we transitioned from the conventional outside-in model of additive manufacturing—where methods and equipment dictate the consumables—to a novel inside-out model, whereby consumables inform the methodology and equipment. Such a paradigm shift will facilitate the development of new functionally graded materials with unique compositions and structural arrangements unattainable through established manufacturing techniques.