Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

ObjectiveTo explore the mechanism of Jiebiao Qingli decoction （JQD） in treating pneumonia caused by influenza A virus （IAV） infection. MethodsA total of 132 Balb/c mice were randomly assigned into normal control （NC）， model control （IAV）， oseltamivir （OSV， 37.5 mg·kg^-1）， and high-， medium-， low-dose JQD （H-， M-， and L-JQD： 6.05， 3.02， and 1.51 g·kg^-1， respectively） groups. The NC group was treated with normal saline nasal drops， and the other groups were intranasally inoculated with A/Brisbane/02/2018 （H1N1） ［pdm09-like virus （H1N1）］ for the modeling of IAV infection. Two hours post-modeling， the NC and IAV groups were administrated with normal saline by gavage， while other groups received corresponding drugs for 7 d. The body mass， survival status， and deaths of mice were recorded daily during the administration of the drugs. On days 3 and 7， the lung index was measured for mice in each group. Pathological changes in the lung tissue were observed via hematoxylin-eosin staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was conducted to measure the viral load （IAV-M） and the mRNA levels of Toll-like receptor 7 （TLR7）， p38 mitogen-activated protein kinase （p38 MAPK）， and nuclear factor-kappa B （NF-κB） in the lung tissue. Western blot was employed to measure the protein levels of p38 MAPK and NF-κB. Enzyme-linked immunosorbent assay was used to quantify serum levels of interleukin-2 （IL-2）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α）. ResultsCompared with the NC group， the IAV group showed reduced survival quality and survival days （P<0.01）， lung congestion， inflammatory cell infiltration， elevated lung index （P<0.01）， increased viral load （P<0.01）， upregulated TLR7， p38 MAPK， and NF-κB levels （P<0.05， P<0.01）， decreased IL-2 level （P<0.01）， and elevated IL-6 and TNF-α levels （P<0.01）. Compared with the IAV group， H-JQD prolonged survival days （P<0.05）. All JQD groups alleviated pathological changes in the lung tissue and reduced the lung index （P<0.01）. M-JQD and H-JQD decreased the viral load （P<0.01）. H-JQD downregulated the mRNA levels of TLR7， p38 MAPK， and NF-κB （P<0.05， P<0.01） and the protein levels of p38 MAPK and NF-κB （P<0.01）， increased the serum IL-2 level （P<0.01）， and lowered the IL-6 and TNF-α levels （P<0.05， P<0.01）. M-JQD downregulated the mRNA level of NF-κB （P<0.01） and the protein level of p38 MAPK （P<0.05）， elevated the IL-2 level （P<0.01）， and lowered the TNF-α level （P<0.01）. ConclusionM- and H-JQD can prevent and control IAV infection-induced pneumonia dose-dependently by inhibiting the TLR7/MAPK/NF-κB signaling pathway， increasing IL-2， and reducing excessive secretion of IL-6 and TNF-α.

ObjectiveTo explore the mechanism of Jiebiao Qingli decoction （JQD） in treating pneumonia caused by influenza A virus （IAV） infection. MethodsA total of 132 Balb/c mice were randomly assigned into normal control （NC）， model control （IAV）， oseltamivir （OSV， 37.5 mg·kg^-1）， and high-， medium-， low-dose JQD （H-， M-， and L-JQD： 6.05， 3.02， and 1.51 g·kg^-1， respectively） groups. The NC group was treated with normal saline nasal drops， and the other groups were intranasally inoculated with A/Brisbane/02/2018 （H1N1） ［pdm09-like virus （H1N1）］ for the modeling of IAV infection. Two hours post-modeling， the NC and IAV groups were administrated with normal saline by gavage， while other groups received corresponding drugs for 7 d. The body mass， survival status， and deaths of mice were recorded daily during the administration of the drugs. On days 3 and 7， the lung index was measured for mice in each group. Pathological changes in the lung tissue were observed via hematoxylin-eosin staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was conducted to measure the viral load （IAV-M） and the mRNA levels of Toll-like receptor 7 （TLR7）， p38 mitogen-activated protein kinase （p38 MAPK）， and nuclear factor-kappa B （NF-κB） in the lung tissue. Western blot was employed to measure the protein levels of p38 MAPK and NF-κB. Enzyme-linked immunosorbent assay was used to quantify serum levels of interleukin-2 （IL-2）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α）. ResultsCompared with the NC group， the IAV group showed reduced survival quality and survival days （P<0.01）， lung congestion， inflammatory cell infiltration， elevated lung index （P<0.01）， increased viral load （P<0.01）， upregulated TLR7， p38 MAPK， and NF-κB levels （P<0.05， P<0.01）， decreased IL-2 level （P<0.01）， and elevated IL-6 and TNF-α levels （P<0.01）. Compared with the IAV group， H-JQD prolonged survival days （P<0.05）. All JQD groups alleviated pathological changes in the lung tissue and reduced the lung index （P<0.01）. M-JQD and H-JQD decreased the viral load （P<0.01）. H-JQD downregulated the mRNA levels of TLR7， p38 MAPK， and NF-κB （P<0.05， P<0.01） and the protein levels of p38 MAPK and NF-κB （P<0.01）， increased the serum IL-2 level （P<0.01）， and lowered the IL-6 and TNF-α levels （P<0.05， P<0.01）. M-JQD downregulated the mRNA level of NF-κB （P<0.01） and the protein level of p38 MAPK （P<0.05）， elevated the IL-2 level （P<0.01）， and lowered the TNF-α level （P<0.01）. ConclusionM- and H-JQD can prevent and control IAV infection-induced pneumonia dose-dependently by inhibiting the TLR7/MAPK/NF-κB signaling pathway， increasing IL-2， and reducing excessive secretion of IL-6 and TNF-α.

Membrane proteins are integral components of cellular membranes, accounting for approximately 30% of the mammalian proteome and serving as targets for 60% of FDA-approved drugs. They are critical to both physiological functions and disease mechanisms. Their functional protein-protein interactions form the basis for many physiological processes, such as signal transduction, material transport, and cell communication. Membrane protein interactions are characterized by membrane environment dependence, spatial asymmetry, weak interaction strength, high dynamics, and a variety of interaction sites. Therefore, in situ analysis is essential for revealing the structural basis and kinetics of these proteins. This paper introduces currently available in situ analytical techniques for studying membrane protein interactions and evaluates the characteristics of each. These techniques are divided into two categories: label-based techniques (e.g., co-immunoprecipitation, proximity ligation assay, bimolecular fluorescence complementation, resonance energy transfer, and proximity labeling) and label-free techniques (e.g., cryo-electron tomography, in situ cross-linking mass spectrometry, Raman spectroscopy, electron paramagnetic resonance, nuclear magnetic resonance, and structure prediction tools). Each technique is critically assessed in terms of its historical development, strengths, and limitations. Based on the authors’ relevant research, the paper further discusses the key issues and trends in the application of these techniques, providing valuable references for the field of membrane protein research. Label-based techniques rely on molecular tags or antibodies to detect proximity or interactions, offering high specificity and adaptability for dynamic studies. For instance, proximity ligation assay combines the specificity of antibodies with the sensitivity of PCR amplification, while proximity labeling enables spatial mapping of interactomes. Conversely, label-free techniques, such as cryo-electron tomography, provide near-native structural insights, and Raman spectroscopy directly probes molecular interactions without perturbing the membrane environment. Despite advancements, these methods face several universal challenges: (1) indirect detection, relying on proximity or tagged proxies rather than direct interaction measurement; (2) limited capacity for continuous dynamic monitoring in live cells; and (3) potential artificial influences introduced by labeling or sample preparation, which may alter native conformations. Emerging trends emphasize the multimodal integration of complementary techniques to overcome individual limitations. For example, combining in situ cross-linking mass spectrometry with proximity labeling enhances both spatial resolution and interaction coverage, enabling high-throughput subcellular interactome mapping. Similarly, coupling fluorescence resonance energy transfer with nuclear magnetic resonance and artificial intelligence (AI) simulations integrates dynamic structural data, atomic-level details, and predictive modeling for holistic insights. Advances in AI, exemplified by AlphaFold’s ability to predict interaction interfaces, further augment experimental data, accelerating structure-function analyses. Future developments in cryo-electron microscopy, super-resolution imaging, and machine learning are poised to refine spatiotemporal resolution and scalability. In conclusion, in situ analysis of membrane protein interactions remains indispensable for deciphering their roles in health and disease. While current technologies have significantly advanced our understanding, persistent gaps highlight the need for innovative, integrative approaches. By synergizing experimental and computational tools, researchers can achieve multiscale, real-time, and perturbation-free analyses, ultimately unraveling the dynamic complexity of membrane protein networks and driving therapeutic discovery.

Background: The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. Methods: MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Results: Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Conclusion Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Background: The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. Methods: MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Results: Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Conclusion Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Background: The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. Methods: MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Results: Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Conclusion Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Background: The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. Methods: MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Results: Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Conclusion Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Child ; Humans ; Mpox (monkeypox)/prevention & control* ; Disease Outbreaks