19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Hospital culture is the sum of common values， codes of conduct， and working methods formed by internal employees within the hospital， and it is the spiritual pillar and core of cohesion of the hospital. Party-building leadership plays an important role in promoting hospital culture construction， including strengthening values guidance， enhancing team cohesion， facilitating management system innovation， and shaping social image and brand value. By analyzing the effectiveness of a series of Party-building activities carried out by Xi’an No. 9 Hospital in recent years， this paper explored the effect and significance of Party-building leadership in promoting hospital culture construction in the new era， as well as proposed guiding strategies for strengthening Party-building work in promoting hospital culture construction in the new era， so as to promote high-quality development of the hospital.

ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

This case report explores the therapeutic potential of theta burst stimulation (TBS) for cognitive enhancement in individuals with brain injuries. The study presents a 38-year-old male suffering from an organic mental disorder attributed to a traumatic brain injury (TBI), who demonstrated notable cognitive improvements following an intensive TBS protocol targeting the left dorsal lateral prefrontal cortex. The treatment led to significant enhancements in impulse control, irritability, and verbal comprehension without adverse effects. Neuropsychological assessments and brain imaging post-intervention revealed improvements in short-term memory, abstract reasoning, list-generating fluency, and increased cerebral blood flow in the prefrontal cortex. These findings suggest that TBS, by promoting neural plasticity and reconfiguring neural networks, offers a promising avenue for cognitive rehabilitation in TBI patients. Further research is warranted to optimize TBS protocols and understand the mechanisms underlying its cognitive benefits.

This case report explores the therapeutic potential of theta burst stimulation (TBS) for cognitive enhancement in individuals with brain injuries. The study presents a 38-year-old male suffering from an organic mental disorder attributed to a traumatic brain injury (TBI), who demonstrated notable cognitive improvements following an intensive TBS protocol targeting the left dorsal lateral prefrontal cortex. The treatment led to significant enhancements in impulse control, irritability, and verbal comprehension without adverse effects. Neuropsychological assessments and brain imaging post-intervention revealed improvements in short-term memory, abstract reasoning, list-generating fluency, and increased cerebral blood flow in the prefrontal cortex. These findings suggest that TBS, by promoting neural plasticity and reconfiguring neural networks, offers a promising avenue for cognitive rehabilitation in TBI patients. Further research is warranted to optimize TBS protocols and understand the mechanisms underlying its cognitive benefits.

This case report explores the therapeutic potential of theta burst stimulation (TBS) for cognitive enhancement in individuals with brain injuries. The study presents a 38-year-old male suffering from an organic mental disorder attributed to a traumatic brain injury (TBI), who demonstrated notable cognitive improvements following an intensive TBS protocol targeting the left dorsal lateral prefrontal cortex. The treatment led to significant enhancements in impulse control, irritability, and verbal comprehension without adverse effects. Neuropsychological assessments and brain imaging post-intervention revealed improvements in short-term memory, abstract reasoning, list-generating fluency, and increased cerebral blood flow in the prefrontal cortex. These findings suggest that TBS, by promoting neural plasticity and reconfiguring neural networks, offers a promising avenue for cognitive rehabilitation in TBI patients. Further research is warranted to optimize TBS protocols and understand the mechanisms underlying its cognitive benefits.

This case report explores the therapeutic potential of theta burst stimulation (TBS) for cognitive enhancement in individuals with brain injuries. The study presents a 38-year-old male suffering from an organic mental disorder attributed to a traumatic brain injury (TBI), who demonstrated notable cognitive improvements following an intensive TBS protocol targeting the left dorsal lateral prefrontal cortex. The treatment led to significant enhancements in impulse control, irritability, and verbal comprehension without adverse effects. Neuropsychological assessments and brain imaging post-intervention revealed improvements in short-term memory, abstract reasoning, list-generating fluency, and increased cerebral blood flow in the prefrontal cortex. These findings suggest that TBS, by promoting neural plasticity and reconfiguring neural networks, offers a promising avenue for cognitive rehabilitation in TBI patients. Further research is warranted to optimize TBS protocols and understand the mechanisms underlying its cognitive benefits.