High consumption of colorful fruits and vegetables correlates with low dementia risk, but the exact molecules and the underlying biological mechanisms governing their bioactive profiles are largely unknown. Using a 10-year observational cohort study coupled with an AI-driven systems pharmacology platform, we identified a natural triterpenoid compound found in colorful fruits and vegetables, α-Amyrin (αA), as a therapeutic candidate for Alzheimer's disease (AD). The efficacy of αA in treating the symptoms of AD, such as Tau tangles, damaged mitochondria, and memory loss, was examined using cross-species models; αA retained memory in AD-like animal models while also strongly inhibiting Tau pathology, especially p-Tau217, in a cellular 'Tau seeding' system and in Tau[P301S] mice, followed by validation using a human 3D microfluidic system. At molecular level, αA is a robust mitochondrial regulator, enhancing mitochondrial stress resilience and activation of mitophagy. Mechanistically, αA inhibits dual leucine zipper kinase (DLK), leading to the inhibition of DLK-Sterile Alpha and TIR Motif Containing 1 (SARM1)-dependent neurodegeneration; this inhibition frees unc-51 Like Autophagy Activating Kinase 1 (ULK1) from the ULK1-SARM1 complex, allowing it to participate in autophagy/mitophagy. αA also shows strong translational potential with a 10.1 h half-life and the ability to cross the blood-brain barrier. Our results indicate that αA may act as a mitochondrial guardian against AD via modulating the DLK-SARM1-ULK1-autophagy/mitophagy axis while further preclinical and clinical studies are warranted.
Carney complex (CNC) is a genetic syndrome predisposing individuals to multiple neoplasms and is characterized by significant clinical heterogeneity. Tumors in bone occur rarely in this disease. When present, they are generally osteochondromyxomas (OMX), a neoplasm almost pathognomonic of CNC. Herein, we report the case of a 21-year-old woman with CNC who presented with an extensive bone lesion in the left temporal bone of the skull, which was surgically removed. It was not an OMX; instead, it was identified as fibrous dysplasia (FD). Additionally, a post-surgical whole-body bone scintigraphy revealed multiple foci of intense radiopharmaceutical uptake in the skull, facial bones, and the right femur, which are still under investigation but may correspond to polyostotic FD and/or multiple OMX. To our knowledge, this is the first report linking FD to CNC in humans, although this is a well-known feature of McCune-Albright syndrome (MAS) and has been described in mice bearing defects of the protein kinase A (PKA), the signaling system affected in both syndromes. Increased PKA activity by defects in GNAS or PRKAR1A, the genes mutated in MAS or CNC, respectively, leads to the proliferation of cells of intermediate differentiation contributing to bone tumor formation. In conclusion, our case underscores the clinical overlap between CNC and MAS and shows that in addition to OMX, FD may also occur in patients with CNC, expanding the clinical spectrum of manifestations in this syndrome.
Nabeel Ahmad,1,* Muhammad Faizan Imran,1,* Rana Talal Ahmed,1 Mirza Muhammad Suleman,1 Madiha Riaz,1 Ahsan Sattar Sheikh,1,* Ming-Hsien Chiang2,* 1Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan; 2Department of Nutritional Science, College of Human Ecology, Fu Jen Catholic University, New Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Ahsan Sattar Sheikh, Institute of Molecular Biology and Biotechnology, The University of Lahore, 1 - km Defence Road, Lahore, Pakistan, Tel +92- 0322-4058338, Email ahsan.sattar@imbb.uol.edu.pk Ming-Hsien Chiang, Department of Nutritional Science, College of Human Ecology, Fu Jen Catholic University, Rm. NF456AB, No. 510, Zhongzheng Road, Xinzhuang Dist, New Taipei, 242062, Taiwan, Tel +886-2-29053541, Fax +886-2-29021215, Email 161642@cloud.fju.edu.twPurpose: The aim of this cross-sectional study was to evaluate the environmental–human interface of antimicrobial resistance (AMR) by investigating drug-resistant bacteria in hospital air and the nasal microbiota of healthcare personnel across four tertiary care hospitals in Pakistan.Material and Methods: A total of 80 samples (40 aerosol samples and 40 nasal swabs) were collected and analyzed using culture-based microbiological identification. Antimicrobial susceptibility testing was performed using the Clinical & Laboratory Standards Institute-guided disc diffusion method, and polymerase chain reaction (PCR) was used to screen representative β-lactam–resistant isolates for key resistance genes, including blaZ, blaI, CTX-M, and SHV.Results: Bacterial isolates were categorized into three ecological groups: environment-exclusive strains (eg, Escherichia coli detected only in aerosols and viridans streptococci detected only in nasal samples), co-existing strains prevalent in both niches (notably Staphylococcus aureus and Staphylococcus epidermidis), and strains showing marked differential prevalence between environments (eg, Serratia marcescens predominant in aerosols and Enterococcus spp. in nasal samples). A high proportion of isolates exhibited resistance to multiple antibiotic classes, consistent with multidrug-resistant (MDR) phenotypes, while resistance patterns suggestive of extensive drug resistance were observed in selected isolates. Molecular analysis confirmed the presence of clinically relevant β-lactamase genes, including blaZ/blaI in aerosol-derived S. aureus and CTX-M/SHV in nasal Klebsiella pneumoniae.Conclusion: These findings demonstrate that hospital air acts as not only a reservoir for environmental pathogens but also a potential conduit for microbial exchange with healthcare personnel. Therefore, integrated infection control strategies incorporating air quality management and personnel surveillance are essential. As the interpretation of the findings is limited by the cross-sectional design and reliance on culture-based methods, future studies should include longitudinal and molecular-based approaches.Plain Language Summary: Why was this study done?The emergence of antibiotic-resistant bacteria is a serious and growing threat to global health. Hospitals cater to many people who are at high risk of infection, and healthcare workers are routinely exposed to antibiotic-resistant bacteria during their daily work. We tried to understand whether hospital air and healthcare staff themselves may contribute to the spread of antibiotic-resistant bacteria within hospital environments.What did the researchers do and find?We collected samples from hospital air and from the nose of 40 healthcare workers across four major hospitals in Pakistan. We identified the bacteria present and tested which antibiotics were still effective against them. We found that some bacteria, such as Staphylococcus aureus, were detected both in the air and among healthcare workers, suggesting possible movement between the environment and staff. Many of these bacteria showed resistance to multiple antibiotics, which can make infections harder to treat. We also identified specific genes that explain why these bacteria are resistant.What do these results mean?Our findings suggest that hospital air and healthcare workers are part of a connected system in which antibiotic-resistant bacteria can circulate. This highlights the importance of protecting both patients and healthcare staff. In addition to surface cleaning, hospitals may benefit from broader infection control strategies, such as improved air management and routine staff monitoring, to reduce the risk of transmission. Keywords: antimicrobial resistance, bacterial infection, molecular epidemiology, environmental health
Two new species, Diapalpus logan sp. n. and Diapalpus riley sp. n., are described from West Africa. They are compared with four other known species of the genus Diapalpus Strand, 1913 (type species is Diapalpus congregarius Strand, 1913). Adults of both sexes, if available, and their genitalia are illustrated, and collection localities are mapped.
Ticks rely on salivary immunomodulators to sustain prolonged blood feeding and transmit pathogens, yet the protein effectors that mediate these processes remain incompletely defined. Here, we characterize three divergent cysteine protease inhibitors—Amacstatins—from the Gulf Coast tick Amblyomma maculatum and delineate their roles in feeding success and Rickettsia parkeri transmission. Integrated transcriptomic, structural, and biochemical analyses reveal that Amacstatin-1, -2, and -3 possess distinct reactive centers, inhibitory selectivity, and tissue-specific expression patterns that are dynamically regulated by blood feeding and rickettsial infection. Silencing all three Amacstatins via RNA interference significantly impaired tick feeding, reducing engorgement, fecundity, and R. parkeri burden in both midgut and salivary glands. Functional assays demonstrated that Amacstatins potently suppress host inflammatory responses, including pro-inflammatory cytokine production, nitric oxide release, and leukocyte recruitment. Together, these findings identify Amacstatins as critical immunomodulatory effectors that promote tick feeding and rickettsial transmission. This work provides a protein-level mechanistic insight into the A. maculatum–R. parkeri interaction and highlights Amacstatins as promising molecular targets for anti-tick and anti-rickettsial strategies.
