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Gradient maturation experiment on hairs implies taphonomic changes in fossil hairs

Science China Earth sciences 2025年第1期68卷 62-73页

作者： Xin LI Yibo ZHOU Tao ZHAO Xingjian HE Yanhong PAN State Key Laboratory for Mineral Deposits Research Center for Critical Earth Material Cycling Centre for Research and Education on Biological Evolution and Environment and Frontiers Science School of Earth Sciences and Engineering Nanjing University Institute of Palaeontology Yunnan Key Laboratory of Earth System Science Yunnan Key Laboratory for PalaeobiologyYunnan University

Mammalian hair, as a key feature related to endothermy, physical protection, and camouflage, has a long geohistorical record that dates back even to the Mesozoic. However, the limited information on the taphonomy of hair hinders the understanding of its evolutionary significance in deep time. To address this, we conducted taphonomic experiments to simulate the transformation process of black hair. The changes in the morphological structure, microscopic characteristics, and chemical composition of hair during the simulated fossilization process were documented by scanning electron microscopy, Fourier transform infrared(FTIR) spectroscopy, and Raman spectroscopy. Our results revealed that damage to the morphology of hair began at a mild temperature(150–175°C), and hair transformed into a fluid-like mass at a relatively high temperature(200°C). In addition, the morphological structure of melanosomes had relatively greater preservation potential than keratins did, and the microscopic features of melanosomes were persistently stable. The Raman and FTIR spectra indicated that the characteristic melanin and keratin peaks changed as the temperature increased. Although the chemical signals were not lost completely, the variations in the characteristic amide bands in the FTIR spectra indicate that the keratins severely degraded at high temperatures(>200°C), whereas the characteristic melanin bands in the Raman spectra suggested that melanin signals were still recognizable, even at high temperatures(>200°C). These results were confirmed by principal component analysis(PCA) and principal component analysis linear discriminant analysis(PCA–LDA). In addition, the Raman signals of all the samples in the simulated experiments were distinguished from the signals of common geological carbonaceous materials(humic acid), which suggested that Raman spectroscopy can be used to detect melanin in fossils.

关键词： Mammalian hair Melanin Keratin Fossilization Experimental taphonomy

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Signaling mechanisms mediated by G-protein coupled receptors in human platelets

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Acta Pharmacologica Sinica 2004年第7期25卷 41-46页

作者： Sheikh Arshad SAEED,Huma RASHEED,Faisal A Wahed FECTO,Mohammad Ilyas ACHAKZAI,Rahmat ALI,John Dennis CONNOR,Anwar-ul-Hassan GILANI Department of biological and biomedical sciences TheAga Khan University Karachi-74800 Pakistan Department of biological and biomedical sciences TheAga Khan University Karachi-74800 Pakistan Department of biological and biomedical sciences TheAga Khan University Karachi-74800 Pakistan Department of biological and biomedical sciences TheAga Khan University Karachi-74800 Pakistan Department of biological and biomedical sciences TheAga Khan University Karachi-74800 Pakistan Department of biological and biomedical sciences TheAga Khan University Karachi-74800 Pakistan Department of biological and biomedical sciences TheAga Khan University Karachi-74800 Pakistan

AIM: The present study deals with the investigation of mechanisms involved in the synergistic interaction between epinephrine and arachidonic acid (AA). METHODS: Venous blood was taken from healthy human volunteers reported to be free of medications for one week. Platelet aggregation was monitored at 37oC using Dual-channel Lumi-aggregometer. The resulting aggregation was recorded for 5 min by the measurement of light transmission as a function of time. RESULTS: The data show that a synergism in platelet aggregation mediated by subthreshold concentrations of epinephrine (1 μmol/L) and AA (0.2 μmol/L) was inhibited by the α2-receptor antagonist (yohimbine, IC50=0.6 μmol/L) and an inhibitor of AA-cyclooxygenase (COX), indomethacin (IC50=0.25 μmol/L). In examining receptor influence on intraplatelet signalling pathways, it was found that the synergistic effect was inhibited by calcium channel blockers, verapamil (IC50=0.4 μmol/L) and diltiazem (IC50=2.5 μmol/L), as well as by low concentrations of inhibitors of phospholipase C (PLC) (U73122; IC50=0.2 μmol/L) and mitogens activated protein kinase (MAPK) (PD 98059; IC50=3.8 μmol/L). Herbimycin A, a specific inhibitor of tyrosine light chain kinase (TLCK), showed inhibition at IC50 value of 15 μmol/L, whereas chelerythrine, a protein kinase C (PKC) inhibitor, had no effect up to 20 μmol/L. CONCLUSION: These data suggest that synergism between epinephrine and AA in platelet aggregation is triggered through receptors coupled to G-protein, which in turn, activate PLC, COX, and MAP kinase-signaling pathways.

关键词： platelet aggregation epinephrine arachidonic acid cyclooxygenase phospholipase C calcium channel blockers nitric oxide MAP kinase

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cGAS-STING: mechanisms and therapeutic opportunities

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Science China Life sciences 2025年

作者： Mengyuan Zhang Changxin Wu Defen Lu Xing Wang Guijun Shang Shanxi Medical University School and Hospital of Stomatology Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials The Key Laboratory of Medical Molecular Cell Biology of Shanxi Province Institutes of Biomedical Sciences Shanxi University College of Life sciences Shanxi Agricultural University

The cGAS-STING pathway plays a crucial role in the innate immune system by detecting mislocalized double-stranded DNA(dsDNA) in the cytoplasm and triggering downstream signal transduction. Understanding the mechanisms by which cGAS and STING operate is vital for gaining insights into the biology of this pathway. This review provides a detailed examination of the structural features of cGAS and STING proteins, with a particular emphasis on their activation and inhibition mechanisms. We also discuss the novel discovery of STING functioning as an ion channel. Furthermore, we offer an overview of key agonists and antagonists of cGAS and STING, shedding light on their mechanisms of action. Deciphering the molecular intricacies of the cGAS-STING pathway holds significant promise for the development of targeted therapies aimed at maintaining immune homeostasis within both innate and adaptive immunity.

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Lung-targeted polyzwitterionic lipid nanoparticles for effective treatment of lung inflammation

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Science China Chemistry 2025年

作者： Wen Zhang Jiaxin Li Nan Wang Muzi Li Chen Peng Xinyue Zhang Guanghui Ouyang Yan Li Beijing Key Laboratory for Bioengineering and Sensing Technology School of Chemistry and Biological Engineering University of Science and Technology Beijing CAS Key Laboratory of Colloid Interface and Chemical Thermodynamics Institute of Chemistry Chinese Academy of Sciences

Lipid nanoparticles (LNPs) are non-viral nucleic acid delivery systems that show great potential in vaccine development and disease treatment. Although LNPs are particularly advantageous for in vivo delivery, the wide application of LNPs is impeded as their systemic delivery of nucleic acid drugs to extrahepatic tissues remains highly challenging. To address this issue, we developed lung-targeted polyzwitterionic LNPs with zwitterionic polymer poly(2-methyacryloyloxyethyl phosphorylcholine)(PMPC) modified 1,2-dimyristoyl-sn-glycerol lipid for the delivery of small interfering RNA (siRNA). Three libraries with 90PMPC-LNPs@siRNA were established. The polyzwitterionic PMPC-LNPs had high siRNA encapsulation efficiency of about90%. The findings revealed that polyzwitterionic PMPC-LNPs@siRNA absorbed protein corona with the main component of Vitronectin, mediating lung-targeted delivery of siRNA. With good cellular uptake and endo/lysosomal escape ability, in vitro and in vivo studies demonstrated that polyzwitterionic PMPC-LNPs with siRNA against tumor necrosis factor-α (TNF-α) could significantly down-regulate the TNF-α in mRNA and protein levels, and improved the pathological features of lung inflammation. Polyzwitterionic PMPC-LNPs@siRNA achieved safe and efficient treatment of lung inflammation. Therefore, this work offered a promising siRNA therapeutic approach for lung diseases.

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Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

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Neural Regeneration Research 2025年第5期20卷 1409-1410页

作者： Rafael Lujan Alejandro Martín-Belmonte Sergi Ferré Francisco Ciruela Synaptic Structure Laboratory Instituto de Biomedicina de la UCLM(IB-UCLM)Departamento de Ciencias MédicasInstituto de Investigación en Salud de Castilla-La Mancha(IDISCAM)Facultad de MedicinaUniversidad Castilla-La ManchaCampus BiosanitarioC/AlmansaAlbaceteSpain Integrative Neurobiology Section National Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA Pharmacology Unit Department of Pathology and Experimental TherapeuticsSchool of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaNeuropharmacology&Pain GroupNeuroscience ProgramBellvitge Institute for Biomedical ResearchL’Hospitalet de LlobregatSpain

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic *** has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

关键词： Alzheimer pathology

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Colorectal cancer carcinogenesis:a review of mechanisms

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Cancer Biology & Medicine 2016年第1期13卷 120-135页

作者： Kanwal Tariq Kulsoom Ghias Department of biological and biomedical sciences Aga Khan University

Colorectal cancer(CRC) is the second most common cancer in women and the third most common in men globally. CRC arises from one or a combination of chromosomal instability, Cp G island methylator phenotype, and microsatellite instability. Genetic instability is usually caused by aneuploidy and loss of heterozygosity. Mutations in the tumor suppressor or cell cycle genes may also lead to cellular transformation. Similarly, epigenetic and/or genetic alterations resulting in impaired cellular pathways, such as DNA repair mechanism, may lead to microsatellite instability and mutator phenotype. Non-coding RNAs, more importantly micro RNAs and long non-coding RNAs have also been implicated at various CRC stages. Understanding the specific mechanisms of tumorigenesis and the underlying genetic and epigenetic traits is critical in comprehending the disease phenotype. This paper reviews these mechanisms along with the roles of various non-coding RNAs in CRCs.

关键词： Colorectal cancer chromosomal instability microsatellite instability non-coding RNA mismatch repair

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Synaptic dysfunction in Alzheimer's disease:the effects of amyloid beta on synaptic vesicle dynamics as a novel target for therapeutic intervention

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Neural Regeneration Research 2018年第4期13卷 616-623页

作者： Jade Marsh Pavlos Alifragis Centre for biomedical sciences School of Biological SciencesRoyal Holloway University of London

The most prevalent form of dementia in the elderly is Alzheimer＇s disease.A significant contributing factor to the progression of the disease appears to be the progressive accumulation of amyloid-β42（Aβ42）,a small hydrophobic ***,attempts to develop therapies targeting the accumulation of Aβ42 have not been successful to treat or even slow down the *** is possible that this failure is an indication that targeting downstream effects rather than the accumulation of the peptide itself might be a more effective *** accumulation of Aβ42 seems to affect various aspects of physiological cell *** this review,we provide an overview of the evidence that implicates Aβ42 in synaptic dysfunction,with a focus on how it contributes to defects in synaptic vesicle dynamics and neurotransmitter *** discuss data that provide new insights on the Aβ42 induced pathology of Alzheimer＇s disease and a more detailed understanding of its contribution to the synaptic deficiencies that are associated with the early stages of the *** the precise mechanisms that trigger synaptic dysfunction are still under investigation,the available data so far has enabled us to put forward a model that could be used as a guide to generate new therapeutic targets for pharmaceutical intervention.

关键词： Alzheimer's disease amyloid-β 42 synaptic vesicles synaptic dysfunction neurotransmitter release

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Eukaryotic cell encystation and cancer cell dormancy:is a greater devil veiled in the details of a lesser evil?

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Cancer Biology & Medicine 2015年第1期12卷 64-67页

作者： Abdul Mannan Baig Naveed Ahmed Khan Farhat Abbas Department of biological and biomedical sciences Aga Khan University

Cancer cell dormancy is the main cause of cancer recurrence and failure of therapy as dormant cells evade not only the anticancer drugs but also the host immune system. These dormant cells veil themselves from detection by imaging and/or using biomarkers, which imposes an additional problem in targeting such cells. A similar form of hibernation process known as encystation is studied in detail for pathogenic unicellular eukaryotic microorganisms. By examination using microarray gene expression profiles, immunocytochemistry tools, and siRNAs during the process of encystation, understanding the covert features of cancer cell dormancy as proposed could be possible. This knowledge can be extended to dormant cancer cells to uncover the mechanisms that underlie this ghost, yet dangerous state of human cancers. We propose a strategy to induce dormancy and exit this state by application of knowledge gained from the encystation induction and retrieval processes in pathogenic eukaryotic microorganisms. Given that early detection and characterization of dormant malignant tumor cells is important as a general strategy to monitor and prevent the development of overt metastatic disease, this homology may enable the design of therapies that could either awake the dormant cell from dormancy to make it available for therapies or prolong such a phase to make cancer appear as a chronic disease

关键词： Cancer cell dormancy cancer recurrence encystation metastasis

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Dynamic modulation of innate immunity programming and memory

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Science China(Life sciences) 2016年第1期59卷 38-43页

作者： Ruoxi Yuan Liwu Li Department of biological Science Pathobiology and Biomedical Sciences Virginia Tech

Recent progress harkens back to the old theme of immune memory, except this time in the area of innate immunity, to which traditional paradigm only prescribes a rudimentary first-line defense function with no memory. However, both in vitro and in vivo studies reveal that innate leukocytes may adopt distinct activation states such as priming, tolerance, and exhaustion, depending upon the history of prior challenges. The dynamic programming and potential memory of innate leukocytes may have far-reaching consequences in health and disease. This review aims to provide some salient features of innate programing and memory, patho-physiological consequences, underlying mechanisms, and current pressing issues.

关键词： innate immunity memory dynamics priming tolerance exhaustion resolving and non-resolving inflammation

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Physarum polycephalum-inspired adaptive optimization design of artificial microtubular networks

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Science China Chemistry 2025年

作者： Si-Min Zeng Di-Wei Zheng Ting Pan Xing-Lan Ding Yun Zhang Chi-Hui Yang Si-Xue Cheng Xian-Zheng Zhang Key Laboratory of biomedical Polymers of Ministry of Education&Department of Chemistry Wuhan University

Natural biological microtubular networks have undergone adaptive evolutionary selection and may offer viable solutions to design challenges in artificial microtubular networks. The plasmodium of the slime mold Physarum polycephalum(P. polycephalum) extends continuously to form a protoplasmic microtubular network structure, directly connecting food *** simulations revealed that the formation of this adaptive P. polycephalum microtubular network could be captured by a mathematical algorithm. Inspired by the P. polycephalum microtubular networks, we propose an adaptive optimization design method for artificial microtubular networks. Specifically, we utilized hydrogels with biodegradable and tissue-adhesive properties to replicate the P. polycephalum microtubular networks via photomask. In Rhodamine B diffusion and glucosecatalyzed reaction experiments, we found that the P. polycephalum microtubular networks exhibited significantly enhanced efficiency compared to vascular and artificial networks. Furthermore, we demonstrated the potential for uric acid(UA) degradation of the hydrogels with a real P. polycephalum microtubular network loaded with urate oxidase(UOx) in a rodent model of hyperuricemia. And this network achieved more than double the effect of the artificial network. This underscores the potential of natural microtubular networks to replace artificial microtubular networks.

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