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Association of promoter polymorphism of the CD14 C (-159) T endotoxin receptor gene with chronic hepatitis B

World Journal of Gastroenterology 2006年第35期12卷 5717-5720页

作者： Amir Houshang Mohammad Alizadeh Mitra Ranjbar Mehrdad Hajilooi Farahnaz Fallahian Research Center for Gastroenterology and Liver Disease ShaheedBeheshti University of Medical Sciences Tehran Iran hamedan university ofmedical sciences hamedan Iran

AIM: To investigate whether single-nucleotide polymor- phisms in the promoter regions of endotoxin-responsive genes CD14 C (-159) T is associated with chronic hepatitis B. METHODS: We obtained genomic DNA from 80 patients with established diagnosis of chronic hepatitis B and 126 healthy subjects served as a control population. The CD 14 C (-159) T polymorphism was investigated using an allele specific PCR method. RESULTS: Twenty seven percent of chronic hepatitis B patients and 75% of controls were heterozygous for CT genotype. The difference between the chronic hepatitis B and control groups was statistically significant [P < 0.0001; Odds ratio (OR) = 2.887; 95% CI: 1.609-5.178]. Twenty four point six percent of chronic hepatitis B and patients 12.3% of the control group were heterozygous for TT genotype. The difference between groups was not statistically significant (P = 0.256; OR = 0.658; 95% CI: 0.319-1.358). Forty eight point four percent of chronic hepatitis B patients and 12.7% of control were homozy- gote for CC genotype (P < 0.004; OR = 0.416; 95% CI: 0.229-0.755). The frequency of allele C was 61.9% and allele T was 38.1% in hepatitis B patients group. The frequency of allele C was 55.2% and allele T was 44.8% for the control group (P = 0.179; OR = 1.319; 95% CI: 0.881-1.977). CONCLUSION: The TT heterozygous genotype was not a risk factor for chronic hepatitis B. CC homozygote genotype is protective for hepatitis B. Lack of heterozy- gosis of genotype CT is a risk factor for chronic hepatitis B. Alleles C or T were not risk factors for chronic hepatitis B. These findings show the role of a single-nucleotide polymorphism at CD14/-159 on the development ofchronic hepatitis B. Endotoxin susceptibility may play a role in the pathogenesis of chronic hepatitis B.

关键词： CD14 C (-159) T gene Single nucleotide polymorphism Chronic hepatitis B Endotoxin susceptibility

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Early identification of stroke through deep learning with multi-modal human speech and movement data

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Neural Regeneration Research 2025年第1期20卷 234-241页

作者： Zijun Ou Haitao Wang Bin Zhang Haobang Liang Bei Hu Longlong Ren Yanjuan Liu Yuhu Zhang Chengbo Dai Hejun Wu Weifeng Li Xin Li School of Computer Science and Engineering Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Neurology Guangdong Neuroscience InstituteGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong ProvinceChina Department of Emergency Medicine Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong ProvinceChina

Early identification and treatment of stroke can greatly improve patient outcomes and quality of *** clinical tests such as the Cincinnati Pre-hospital Stroke Scale(CPSS)and the Face Arm Speech Test(FAST)are commonly used for stroke screening,accurate administration is dependent on specialized *** this study,we proposed a novel multimodal deep learning approach,based on the FAST,for assessing suspected stroke patients exhibiting symptoms such as limb weakness,facial paresis,and speech disorders in acute *** collected a dataset comprising videos and audio recordings of emergency room patients performing designated limb movements,facial expressions,and speech tests based on the *** compared the constructed deep learning model,which was designed to process multi-modal datasets,with six prior models that achieved good action classification performance,including the I3D,SlowFast,X3D,TPN,TimeSformer,and *** found that the findings of our deep learning model had a higher clinical value compared with the other ***,the multi-modal model outperformed its single-module variants,highlighting the benefit of utilizing multiple types of patient data,such as action videos and speech *** results indicate that a multi-modal deep learning model combined with the FAST could greatly improve the accuracy and sensitivity of early stroke identification of stroke,thus providing a practical and powerful tool for assessing stroke patients in an emergency clinical setting.

关键词： artificial intelligence deep learning diagnosis early detection FAST screening stroke

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Potential role of tanycyte-derived neurogenesis in Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1599-1612页

作者： Guibo Qi Han Tang Jianian Hu Siying Kang Song Qin Department of Anatomy Histologyand EmbryologySchool of Basic Medical SciencesFudan UniversityShanghaiChina State Key Laboratory of medical Neurobiology and MOE Frontiers Center for Brain Science Fudan UniversityShanghaiChina

Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. Intriguingly,metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore,the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood–brain barrier ***, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could pro

关键词： Alzheimer's disease blood–brain barrier ependymoglial cells hypothalamus metabolic diseases neural stem cells neurogenesis neuroinflammatory diseases neurons tanycyte

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Prevalence of hepatitis C virus infection and its related risk factors in drug abuser prisoners in hamedan-Iran

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World Journal of Gastroenterology 2005年第26期11卷 4085-4089页

作者： Amir Houshang Mohammad Alizadeh Seyed Moayed Alavian Khalil Jafari Nastaran Yazdi Research Center for Gastroenterology and Liver Disease Shaheed Beheshti university of medical sciences Tehran Iran Baghiatalah university of medical sciences Tehran Iran hamedan university of medical sciences hamedan Iran

AIM:Recent studies in Iran has shown that prevalence of hepatitis C virus (HCV) infection among Iranian prisoners is high, in spite of low HCV seroprevalence in general population. METHODS: This study was carried out in the central prison of hamedan - Iran, in year 2002. Inmates were interviewed using a standard questionnaire including demographic, imprisonment history and HCV-related risk behaviors items. Thereafter, the sera drawn from the participants were tested for anti-HIV and anti-HCV antibodies. RESULTS: A total number of 427 drug abuser inmates participated in our study. Three hundred and ninety-seven (93%) were men and 30 (7%) were women. Total number of IV drug abusers (IDA) and non-IV drug abusers (NIDA) was 149 (34.9%) and 278 (65.1%), respectively. The overall rate of antibody positivity among inmates was 0.9% for HIV and 30% for HCV. Of all IDAs, 31.5% and of NIDAs, 29.1% had serological evidence of HCV infection. CONCLUSION: The seroprevalence of HCV infection among drug abuser prisoners in comparison with the general population in Iran, is very high (30% vs in italics 0.2%). Our results indicate the importance of policies to prevent transmission of HCV infection during and following incarceration.

关键词： Hepatitis C virus Prisoners Drug abusers Iran

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Deciphering fungal metabolon coupling tandem inverse-electrondemand Diels-Alder reaction and semipinacol rearrangement for the biosynthesis of spiro polycyclic alkaloids

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Science China Chemistry 2025年第1期68卷 288-296页

作者： Shuai Liu Wen-Qiang Xu Ying-Tong Di Man-Cheng Tang Ding-Kang Chen Ming-Ming Cao Yao-Wen Chang Hong-Yu Tang Chun-Mao Yuan Jun-Bo Yang Zhi-Li Zuo Han Guo Zi-Fei Xu Ying Zeng Yun-Dong Wu Xiao-Jiang Hao Key Laboratory of Phytochemistry and Natural Medicines (Chinese Academy of sciences) Kunming Institute of Botany Chinese Academy of Sciences university of Chinese Academy of sciences Lab of Computational Chemistry and Drug Design State Key Laboratory of Chemical Oncogenomics Peking University Shenzhen Graduate School Shenzhen Bay Laboratory State Key Laboratory of Microbial Metabolism School of Life Sciences & Biotechnology Shanghai Jiao Tong University State Key Laboratory of Functions and Applications of Medicinal Plants Guizhou Medical University Molecular Biology Experimental Center Germplasm Bank of Wild Species in Southwest China Kunming Institute of Botany Chinese Academy of Sciences Yunnan Key Laboratory for Wild Plant Resources Kunming Institute of Botany Chinese Academy of Sciences Research Unit of Chemical Biology of Natural Anti-Virus Products Chinese Academy of Medical Sciences

In the intricate process of natural product biosynthesis, a metabolon can enhance metabolic flux by associating sequential enzymes. A fungal metabolon, comprising of flavin-dependent monooxygenase Spe F and P450 monooxygenase Spe G, is identified in the biosynthesis of spiro polycyclic alkaloids(+)-notoamide B and its diastereomer(+)-versicolamide B. Using notoamide E as a substance, Spe F/Spe G metabolon can control the stereoselectivity of its 2,3-epoxidation, followed by hydrogen atom ion at C-17 to generate reactive epoxide tau-m A with dienyl iminium unit. Subsequently,(+)-notoamide B and(+)-versicolamide B are produced via tandem nonenzymatic inverse-electron-demand Diels-Alder reaction and semipinacol rearrangement. This provides the first example of metabolon in the biosynthesis of spiro-prenylated indole alkaloids.

关键词： metabolon Diels-Alder reaction semipinacol rearrangement biosynthesis notoamides spiro polycyclic alkaloids

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Neuroprotective potential for mitigating ischemia-reperfusion-induced damage

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Neural Regeneration Research 2025年第8期20卷 2199-2217页

作者： Zi Ye Runqing Liu Hangxing Wang Aizhen Zuo Cen Jin Nan Wang Huiqi Sun Luqian Feng Hua Yang The Clinical medical College Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Division of Infectious Diseases Department of Internal MedicinePeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina School of medical Imaging Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Division of Gastroenterology First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina The Second Clinical medical College Lanzhou UniversityLanzhouGansu ProvinceChina Department of Neurosurgery Affiliated Hospital of Guizhou Medical UniversityGuiyangGuizhou ProvinceChina

Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion *** studies have elucidated the neuroprotective role of the sirtuin protein family(Sirtuins)in modulating cerebral ischemia-reperfusion ***,the potential of utilizing it as a novel intervention target to influence the prognosis of cerebral ischemia-reperfusion injury requires additional *** this review,the origin and research progress of Sirtuins are summarized,suggesting the involvement of Sirtuins in diverse mechanisms that affect cerebral ischemia-reperfusion injury,including inflammation,oxidative stress,blood-brain barrier damage,apoptosis,pyroptosis,and *** therapeutic avenues related to Sirtuins that may improve the prognosis of cerebral ischemia-reperfusion injury were also investigated by modulating Sirtuins expression and affecting representative pathways,such as nuclear factor-kappa B signaling,oxidative stress mediated by adenosine monophosphate-activated protein kinase,and the forkhead box *** review also summarizes the potential of endogenous substances,such as RNA and hormones,drugs,dietary supplements,and emerging therapies that regulate Sirtuins *** review also reveals that regulating Sirtuins mitigates cerebral ischemia-reperfusion injury when combined with other risk *** Sirtuins show promise as a potential target for the treatment of cerebral ischemiareperfusion injury,most recent studies are based on rodent models with circadian rhythms that are distinct from those of humans,potentially influencing the efficacy of Sirtuinstargeting drug ***,this review provides new insights into the role of Sirtuins in the pathology and treatment of cerebral ischemia-reperfusion injury.

关键词： apoptosis autophagy blood-brain barrier dietary supplements drug hormones inflammation neuroprotection oxidative stress prognosis pyroptosis reperfusion injury risk factors RNA therapeutics

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AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis

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Science China Life sciences 2025年第1期68卷 204-218页

作者： Chen Xiong Hong Ling Yingdan Huang Hanzhi Dong Bangxiang Xie Qian Hao Xiang Zhou Fudan university Shanghai Cancer Center and Institutes of Biomedical sciences Fudan University Department of Oncology Shanghai Medical CollegeFudan University Department of Breast Surgery Fudan University Shanghai Cancer CenterFudan University Department of Oncology First Affiliated Hospital of Nanchang University Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical University Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer Key Laboratory of Breast Cancer in Shanghai Fudan University Shanghai Cancer CenterFudan University Shanghai Key Laboratory of medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan University

Tumor suppressor p53-mediated cell cycle arrest and DNA damage repair may exert cytoprotective effects against cancer therapies, including WEE1 inhibition. Considering that p53 activation can also lead to multiple types of cell death, the role of this tumor suppressor in WEE1 inhibitor-based therapies remains disputed. In this study, we reported that nucleolar stress-mediated p53 activation enhanced the WEE1 inhibitor AZD1775-induced ferroptosis to suppress lung cancer growth. Our findings showed that AZD1775 promoted ferroptosis by blocking cystine uptake, an action similar to that of Erastin. Meanwhile, inhibition of WEE1 by the WEE1 inhibitors or si RNAs induced compensatory upregulation of SLC7A11, which conferred resistance to ferroptosis. Mechanistically, AZD1775 prevented the enrichment of H3K9me3, a histone marker of transcriptional repression, on the SLC7A11 promoter by repressing the expression of the histone methyltransferase SETDB1, thereby enhancing NRF2-mediated SLC7A11 transcription. This finding was also validated using the H3K9me3 inhibitor BRD4770. Remarkably, we found that the nucleolar stress-inducing agent Actinomycin D(Act. D) inhibited SLC7A11 expression by activating p53, thus augmenting AZD1775-induced ferroptosis. Moreover, the combination of AZD1775 and Act. D synergistically suppressed wild-type p53-harboring lung cancer cell growth both in vitro and in vivo. Altogether, our study demonstrates that AZD1775 promotes ferroptosis by targeting cystine uptake but also mediates the adaptive activation of SLC7A11 through the WEE1-SETDB1 cascade and NRF2-induced transcription, and inhibition of SLC7A11 by Act. D boosts the anti-tumor efficacy of AZD1775 by enhancing ferroptosis in cancers with wild-type p53.

关键词： p53 NRF2 SLC7A11 WEE1 AZD1775 ferroptosis nucleolar stress

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Breaking new ground in photocatalysis: lutetium texaphyrin as a trigger for pyroptosis through biomolecular photoredox reactions

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Science China Chemistry 2025年第1期68卷 1-2页

作者： Qihang Ding Mengrong He Meijia Gu Department of Chemistry Korea University Department of Ultrasound Medicine Union Hospital Tongji Medical College Huazhong University of Science and Technology Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE) School of Pharmaceutical Sciences Wuhan University

Malignant neoplasms consistently pose a significant threat to global public health [1,2]. In recent years, immunotherapy has demonstrated remarkable clinical success; however, its efficacy is limited by the scarcity of immune cell infiltration within tumor microenvironments. Cell pyroptosis, a gasdermin-mediated process characterized by cellular swelling,rupture, and the release of intracellular contents such as IL-1β, IL-18, ATP, HMGB1, plays a crucial role in this context[3,4].

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Small modifications of endo-functionalized cavities lead to large changes in molecular interaction in water

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Science China Chemistry 2025年第1期68卷 369-376页

作者： Song-Meng Wang Hao Nian Yan-Fang Wang Li-Shuo Zheng Yu-Tao Zheng Yi-Wei Dong Liping Huang Xiaoping Wang Wei Jiang Liu-Pan Yang Department of Chemistry Southern University of Science and Technology School of Chemistry and Pharmaceutical sciences State Key Laboratory for Chemistry and Molecular Engineering of Medicinal ResourcesGuangxi Normal University School of Pharmaceutical Science Hengyang Medical School University of South China

Studying molecular recognition in aqueous environments is crucial for understanding biological processes. Herein, we present a series of N-doped endo-functionalized anthracene-based cavities by introducing inward-directed pyridine units. The subtle modifications can significantly affect the binding properties of these receptors, which is similar to the mutations in biological systems. Combining theoretical calculations and molecular recognition experiments demonstrated that these “mutations” have an impact on the hydrophobicity and charge distribution of the hosts, consequently significantly influencing molecular *** is crucial for understanding the intricate mechanisms of molecular-level interactions in biological receptors.

关键词： host-guest interaction hydrophobic effect endo-functionalized cavity mutation pyridine

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Remaking a connection:molecular players involved in post-injury synapse formation

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Neural Regeneration Research 2025年第6期20卷 1719-1720页

作者： Diogo Tomé Ramiro D.Almeida iBiMED-Institute of Biomedicine Department of Medical SciencesUniversity of AveiroAveiroPortugal CNC-Center for Neuroscience and Cell Biology University of CoimbraCoimbraPortugal

Functional recovery from central nervous system(CNS)trauma depends not only on axon regeneration or compensatory sprouting of uninjured fibers but also on the ability of newly grown axons to establish functional synapses with appropriate *** several studies have successfully promoted long-distance axonal regeneration in distinct CNS injury models,none of them have resulted in a viable therapeutic approach for patient recovery.A possible reason may be the lack of new synaptogenesis for reestablishing the circuitry lost after ***,we discuss how our understanding of the mechanisms that instruct synapse formation in the injured nervous system may contribute to the design of new strategies to promote functional restoration in traumatic CNS disorders.

关键词： viable injury instru

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