关键词：
RNA m6A modification;Programmed cell deaths (PCD);Bifurcation role of YTHDF2;Environmental stress and m6A regulation;Fluorene-9-bisphenol (BHPF)
摘要：
N-6-methyladenosine (m(6)A) is a critical regulator in the fate of RNA, but whether and how m(6)A executes its functions in different tissues remains largely obscure. Here we report downregulation of a crucial m(6)A reader, YTHDF2, leading to tissue-specific programmed cell deaths (PCDs) upon fluorene-9-bisphenol (BHPF) exposure. Currently, Bisphenol A (BPA) substitutes are widely used in plastic manufacturing. Interrogating eight common BPA substitutes, we detected BHPF in 14% serum samples of pregnant participants. In a zebrafish model, BHPF caused tissue-specific PCDs triggering cardiac and vascular defects. Mechanistically, BHPF-mediated downregulation of YTHDF2 reduced YTHDF2-facilitated translation of m(6)A-gch1 for cardiomyocyte ferroptosis, and decreased YTHDF2-mediated m(6)A-sting1 decay for caudal vein plexus (CVP) apoptosis. The two distinct YTHDF2-mediated m(6)A regulations and context-dependent co-expression patterns of gch1/ythdf2 and tnfrsf1a/ythdf2 contributed to YTHDF2-mediated tissue-specific PCDs, uncovering a new layer of PCD regulation. Since BHPF/YTHDF2-medaited PCD defects were also observed in mammals, BHPF exposure represents a potential health threat.
通讯机构：
[Xilin Xiao] S;School of Chemistry and Chemical Engineering, School of Resource & Environment and Safety Engineering, School of Public Health, Hunan Key Laboratory for the Design and Application of Actinide Complexes, University of South China, Hengyang, Hunan 421001, P. R. China<&wdkj&>State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha, Hunan 410082, P. R. China
摘要：
A convenient and portable smartphone-assisted method for the colorimetric detection of uranyl ions (UO22+) in aqueous solutions is proposed using rifampicin and 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol (Br-PADAP) as chromogenic agents. The addition of UO22+ would cause reaction with chromogenic agents to form complexes, changing the colour from orange to dark red in the rifampicin system and from yellow to light pink in the Br-PADAP system. To achieve the on-site estimation of the trace UO22+ concentration range, digital images of colour changes captured by the smartphone under fixed lighting conditions were imported into the built-in application named "Detect" to obtain HSV (hue, saturation, and value) and HSL (hue, saturation, lightness) information, which could be associated with the concentration of uranyl ions. For more precise laboratory-level detection, ultraviolet-visible (UV-vis) spectroscopy was employed as well. The absorbance of the rifampicin system exhibited strong linearity with the UO22+ concentration in the range from 4 to 50 mu M at 375 nm with a method detection limit (MDL) of 3.17 mu M by the UV-vis-based method, while that of Br-PADAP system had a linear relationship with the concentration from 0.9 to 7 mu M at 562 nm with an MDL of 0.89 mu M. The two strategies may be combined to detect UO22+ across a larger concentration range, and this method has been successfully used to analyze real samples including soil around uranium mines.
期刊：
International Immunopharmacology,2023年116:109780 ISSN：1567-5769
通讯作者：
Li, Yumeng;Long, Dingxin
作者机构：
[Li, Zhenyu; Long, Dingxin] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China.;[Li, Zhenyu; Zheng, Kang; He, Siqin; He, Zhangping] Univ South China, Inst Pathogen Biol, Sch Basic Med, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Wang, Yan] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Operating Room, Hengyang 421001, Peoples R China.;[Lu, Xianzhou] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Li, Yumeng] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Clin Lab Med, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Long, Dingxin] H;[Li, Yumeng] D;Department of Clinical Laboratory Medicine, The First Affiliated Hospital of University of South China, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China. Electronic address:;Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China. Electronic address:
摘要：
Although photothermal therapy (PTT) employing nanozymes has shown excellent antibacterial potential, excessive heating generally harms host cells and hinders recovery. Herein, we report an innovative technique for acquiring the programmed temperature by managing the catalytic activity of nanozymes. The photothermal system of CeO2 + F− + TMB can obtain precise photothermal temperature by adjusting the concentration of fluoride ions under near-infrared irradiation. At the optimized photothermal temperature, the photothermal system affords fine photothermal antibacterial treatment with high-efficiency antibacterial effects against Staphylococcus aureus and Escherichia coli in vitro. In vivo wound healing experiments confirm that the system can effectively promote fibroblast proliferation, angiogenesis and collagen deposition with remarkable wound healing efficiency. This strategy offers a novel design concept for creating a new generation of PTT and opens the way for the creation of alternative antibiotics.
作者机构：
[Pei, Xinrong; Luo, Feiya; Sun, Lei; Xing, Shuxia] Natl Inst Food & Drug Control, Beijing 100052, Peoples R China.;[Li, Xiaoling; Hu, Fangyan; Long, Dingxin; Hu, Zehui] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Li, Xiaoling; Hu, Fangyan; Long, Dingxin; Hu, Zehui] Univ South China, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China.
通讯机构：
[Dingxin Long; Lei Sun] A;Authors to whom correspondence should be addressed.<&wdkj&>School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China<&wdkj&>Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang Medical School, University of South China, Hengyang 421001, China<&wdkj&>Authors to whom correspondence should be addressed.<&wdkj&>National Institutes for Food and Drug Control, Beijing 100052, China
摘要：
The prevalence of Alzheimer's disease (AD) is significantly increasing due to the aging world population, and the currently available drug treatments cannot cure or even slow its progression. alpha-lipoic acid (LA) is a biological factor widely found in spinach and meat and can dissolve in both lipid and aqueous phases. In medicine, LA has been shown to reduce the symptoms of diabetic polyneuropathy, acute kidney injury, cancers, and some metabolism-related diseases. This study to proves that alpha-lipoic acid (LA) can stabilize the cognitive function of patients with Alzheimer's disease (AD). BV2 cells were divided into control, LA, A beta(25-35), and LA + A beta(25-35) groups. Cell growth; IL-6, IL-1 beta, TNF-alpha, IFN-gamma, SOD, GPx, CAT, ROS, NO, and iNOS secretion; Wnt-related proteins; cell apoptosis; and cell activation were examined. Here, we found that LA could effectively repress apoptosis and changes in the morphology of microglia BV2 cells activated by A beta(25-35), accompanied by the inhibition of the inflammatory response induced by A beta(25-35.) The Wnt/beta-catenin pathway is also involved in preventing A beta(25-35)-induced cytotoxicity in microglia by LA. We found an inhibitory effect of LA on microglia toxicity induced by A beta(25-35), suggesting that a combination of anti-inflammatory and antioxidant substances may offer a promising approach to the treatment of AD.
通讯机构：
[Pingkun Zhou] D;Department of Radiation Biology, Beijing Key Laboratory for Radiobiology (BKLRB), Beijing Institute of Radiation Medicine, Taiping Road 27th, Haidian District, Beijing 100850, China<&wdkj&>Department of Preventive Medicine, School of Public Health, University of South China, Changsheng West Road 28th, Zhengxiang District, Hengyang 421001, China<&wdkj&>Author to whom correspondence should be addressed.
摘要：
DNA damage in astronauts induced by cosmic radiation poses a major barrier to human space exploration. Cellular responses and repair of the most lethal DNA double-strand breaks (DSBs) are crucial for genomic integrity and cell survival. Post-translational modifications (PTMs), including phosphorylation, ubiquitylation, and SUMOylation, are among the regulatory factors modulating a delicate balance and choice between predominant DSB repair pathways, such as non-homologous end joining (NHEJ) and homologous recombination (HR). In this review, we focused on the engagement of proteins in the DNA damage response (DDR) modulated by phosphorylation and ubiquitylation, including ATM, DNA-PKcs, CtIP, MDM2, and ubiquitin ligases. The involvement and function of acetylation, methylation, PARylation, and their essential proteins were also investigated, providing a repository of candidate targets for DDR regulators. However, there is a lack of radioprotectors in spite of their consideration in the discovery of radiosensitizers. We proposed new perspectives for the research and development of future agents against space radiation by the systematic integration and utilization of evolutionary strategies, including multi-omics analyses, rational computing methods, drug repositioning, and combinations of drugs and targets, which may facilitate the use of radioprotectors in practical applications in human space exploration to combat fatal radiation hazards.
关键词：
DNA damage response;PARP1;chromatin accessibility;m(6)A methylation;radiosensitivity
摘要：
Chromatin remodeling and N(6)-methyladenosine (m(6)A) modification are two critical layers in controlling gene expressionand DNA damage signaling in most eukaryotic bioprocesses. Here, we report that poly(ADP-ribose) polymerase 1 (PARP1) controls the chromatin accessibility of METTL3 to regulate its transcription and subsequent m(6)A methylation of poly(A)(+) RNA in response to DNA damage induced by radiation. The transcription factors nuclear factor I-C (NFIC) and TATA binding protein (TBP) are dependent on PARP1 to access the METTL3 promoter to activate METTL3 transcription. Upon irradiation or PARP1 inhibitor treatment, PARP1 disassociated from METTL3 promoter chromatin, which resulted in attenuated accessibility of NFIC and TBP and, consequently, suppressed METTL3 expression and RNA m(6)A methylation. Lysophosphatidic Acid Receptor 5(LPAR5) mRNA was identified as a target of METTL3, and m(6)A methylation was located at A1881. The level of m(6)A methylation of LPAR5 significantly decreased, along with METTL3 depression, in cells after irradiation or PARP1 inhibition. Mutation of the LPAR5 A1881 locus in its 3' UTR results in loss of m(6)A methylation and, consequently, decreased stability of LPAR5 mRNA. METTL3-targeted small-molecule inhibitors depress murine xenograft tumor growth and exhibit a synergistic effect with radiotherapy invivo. These findings advance our comprehensive understanding of PARP-related biological roles, which may have implications for developing valuable therapeutic strategies for PARP1 inhibitors in oncology.
期刊：
Frontiers in Microbiology,2023年14:1270431 ISSN：1664-302X
通讯作者：
Xu, ZQ;Long, XZ
作者机构：
[Xu, Zhiqiang; Wang, Hui; Xu, ZQ] Xian Univ Technol, State Key Lab Ecohydraul Northwest Arid Reg, Xian, Peoples R China.;[Li, Yu; Liu, Bo; Zhai, Pengxiang; Ma, Jianghang; Xu, Zhiqiang; Wang, Hui; Xu, ZQ] Xian Univ Technol, Sch Water Resources & Hydroelect Engn, Dept Municipal & Environm Engn, Xian, Peoples R China.;[Long, Xizi] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Key Lab Typ Environm Pollut & Hlth Hazards Hunan P, Hengyang, Peoples R China.
通讯机构：
[Long, XZ ] U;[Xu, ZQ ] X;Xian Univ Technol, State Key Lab Ecohydraul Northwest Arid Reg, Xian, Peoples R China.;Xian Univ Technol, Sch Water Resources & Hydroelect Engn, Dept Municipal & Environm Engn, Xian, Peoples R China.;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Key Lab Typ Environm Pollut & Hlth Hazards Hunan P, Hengyang, Peoples R China.
关键词：
biocathode;cathodic reduction;electron transfer;heavy metal wastewater;microbial fuel cell
摘要：
Various types of electroactive microorganisms can be enriched to form biocathodes that reduce charge-transfer resistance, thereby accelerating electron transfer to heavy metal ions with high redox potentials in microbial fuel cells. Microorganisms acting as biocatalysts on a biocathode can reduce the energy required for heavy metal reduction, thereby enabling the biocathode to achieve a lower reduction onset potential. Thus, when such heavy metals replace oxygen as the electron acceptor, the valence state and morphology of the heavy metals change under the reduction effect of the biocathode, realizing the high-efficiency treatment of heavy metal wastewater. This study reviews the mechanisms, primary influencing factors (e.g., electrode material, initial concentration of heavy metals, pH, and electrode potential), and characteristics of the microbial community of biocathodes and discusses the electron distribution and competition between microbial electrodes and heavy metals (electron acceptors) in biocathodes. Biocathodes reduce the electrochemical overpotential in heavy metal reduction, permitting more electrons to be used. Our study will advance the scientific understanding of the electron transport mechanism of biocathodes and provide theoretical support for the use of biocathodes to purify heavy metal wastewater.
通讯机构：
[Xu, LZ; Niu, XH ; Pan, JM] J;Jiangsu Univ, Sch Agr Engn, Zhenjiang 212013, Peoples R China.;Jiangsu Univ, Sch Chem & Chem Engn, Zhenjiang 212013, Peoples R China.;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang 421001, Peoples R China.
摘要：
Nanozyme-based multimode detection is a useful means to improve the accuracy and stability of analytical methods. However, both multifunctional nanozymes and related multimodal sensing strategies are still very scarce. Besides, they require complex processes to fabricate and operate. To fill this gap, here we propose a spontaneous interfacial in situ growth strategy to prepare a new bifunctional material (CePO(4):Tb@MnO(x)) featuring good oxidase-like activity and green photoluminescence for the dual-mode colorimetric/luminescence determination of ascorbic acid (AA)-related biomarkers specifically. CePO(4):Tb@MnO(x) was gained through the controllable redox reaction between KMnO(4) and CePO(4):Tb nanorods. It was interestingly found that MnO(x) in situ growth not only significantly enhanced the enzyme-like activity but also could reversibly regulate the luminescence of CePO(4):Tb via a dual quenching mechanism. More interestingly, CePO(4):Tb@MnO(x) exhibited a distinctive response toward AA against other reducing species. A double-coordination regulation mechanism was further verified to clarify the catalytic activity and luminescence switching behaviors in CePO(4):Tb@MnO(x). Based on these findings, a dual-mode colorimetric/luminescence approach was established for AA sensing in a "one-stone-two-birds" manner, providing excellent selectivity, sensitivity, and practicability. Furthermore, the determination of AA-related biomarkers, including acid phosphatase activity and organophosphorus residue, was also validated by the sensing principle. Our work not only deepens the understanding of the coordinated regulation of the luminescence and enzyme-like features in lanthanide-based materials but also offers a novel way to design and develop multifunctional nanozymes for advanced bioanalytical applications.
期刊：
International Journal of Biological Macromolecules,2023年252:126500 ISSN：0141-8130
通讯作者：
Chen, LL;Bai, YL
作者机构：
[Pu, Chunmin; Chen, Lili; Liao, Xiaoyan] Univ South China, Coll Publ Hlth, Hengyang Med Sch, Dept Publ Hlth Lab Sci, 28 Changsheng West Rd, Hengyang 421001, Hunan, Peoples R China.;[Pu, Chunmin; Bai, Yalong; Liao, Xiaoyan] Shanghai Acad Agr Sci, Inst Agrifood Stand & Testing Technol, 1000 Jinqi Rd, Shanghai 201403, Peoples R China.;[Shi, Xianming; Cui, Yan] Shanghai Jiao Tong Univ, MOST USDA Joint Res Ctr Food Safety, Sch Agr & Biol, State Key Lab Microbial Metab, Shanghai 200240, Peoples R China.
通讯机构：
[Chen, LL ] U;[Bai, YL ] S;Univ South China, Coll Publ Hlth, Hengyang Med Sch, Dept Publ Hlth Lab Sci, 28 Changsheng West Rd, Hengyang 421001, Hunan, Peoples R China.;Shanghai Acad Agr Sci, Inst Agrifood Stand & Testing Technol, 1000 Jinqi Rd, Shanghai 201403, Peoples R China.
关键词：
Agarose gel;Amino-modified magnetic particles;Aptamer;DNA extraction;Short single-stranded DNA
摘要：
With the rapid advancements in aptamer screening, the efficient extraction of short single-stranded DNA (ssDNA) from agarose gel has become a new requirement. However, the currently available products are primarily designed for double-stranded DNA (dsDNA) and exhibit limited efficacy when applied to the extraction of short ssDNA. In this study, we successfully developed a novel method based on amino-modified silica-coated magnetic particles (ASMPs) for the extraction of short ssDNA from agarose gel. The gel slices containing short ssDNA were subjected to centrifugation in a spin column/centrifugation tube assembly with silica wool, followed by the adsorption using ASMPs. Subsequently, reagents containing phosphate groups were employed to desorb ssDNA from the surface of ASMPs. Through optimization of each step, we realized remarkable efficiency in the extraction of short ssDNA. To assess the efficacy of our method, we utilized it in aptamer screening. The results demonstrated that our method outperformed three commercially available DNA gel extraction products (Q-kit, S-kit, and V-kit). The relative recovery rates of all methods were as follows: M-dNTP (100.00%)>M-BB (63.38%)>Q-kit (46.64%)>S-kit (15.98%)>V-kit (0.38%). The results strongly suggest that the developed method holds promise for short ssDNA extraction from agarose gel.
通讯机构：
[Wang, FD ; Wang, YZ ] Z;Zhejiang Univ, Coll Anim Sci, Key Lab Mol Anim Nutr, Minist Educ, Hangzhou, Peoples R China.;Minist Agr, Key Lab Anim Nutr & Feed Sci Eastern China, Hangzhou, Zhejiang, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Publ Hlth, State Key Lab Expt Hematol,Sch Med, Hangzhou, Peoples R China.;Univ South China, Affiliated Hosp 1, Sch Publ Hlth, Hengyang Med Sch,Basic Med Sci, Hengyang, Peoples R China.
摘要：
As a family of cationic host defense peptides, defensins are mainly synthesized by Paneth cells, neutrophils, and epithelial cells, contributing to host defense. Their biological functions in innate immunity, as well as their structure and activity relationships, along with their mechanisms of action and therapeutic potential, have been of great interest in recent years. To highlight the key research into the role of defensins in human and animal health, we first describe their research history, structural features, evolution, and antimicrobial mechanisms. Next, we cover the role of defensins in immune homeostasis, chemotaxis, mucosal barrier function, gut microbiota regulation, intestinal development and regulation of cell death. Further, we discuss their clinical relevance and therapeutic potential in various diseases, including infectious disease, inflammatory bowel disease, diabetes and obesity, chronic inflammatory lung disease, periodontitis and cancer. Finally, we summarize the current knowledge regarding the nutrient-dependent regulation of defensins, including fatty acids, amino acids, microelements, plant extracts, and probiotics, while considering the clinical application of such regulation. Together, the review summarizes the various biological functions, mechanism of actions and potential clinical significance of defensins, along with the challenges in developing defensins-based therapy, thus providing crucial insights into their biology and potential clinical utility.
作者机构：
[Yang, Yunyin; Lv, Yitao; Li, Jingyan; Zhang, Yi; Zhang, Min] Northwest A&F Univ, Coll Food Sci & Engn, Yangling 712100, Shaanxi, Peoples R China.;[Wang, Jiacheng] Yangzhou Univ, Med Coll, Yangzhou 225009, Jiangsu, Peoples R China.;[Xiao, Xilin] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Dept Publ Hlth Lab Sci, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Xilin Xiao] D;[Min Zhang] C;College of Food Science and Engineering, Northwest A&F University, 22 Xinong Road, Yangling, Shaanxi 712100, China<&wdkj&>Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
通讯机构：
[Yang, HF ] U;[Cai, R ] H;Hunan Univ, Coll Mat Sci & Engn, Coll Chem & Chem Engn, Coll Biol,Mol Sci & Biomed Lab,State Key Labr Chem, Changsha 410082, Peoples R China.;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Key Lab Typ Environm Pollut & Hlth Hazards, Hengyang 421001, Peoples R China.
摘要：
Novel and effective coreaction accelerators are of great importance in electrochemiluminescence (ECL) systems. In this work, novel AuPt nanodonuts, i.e., SnS2 quantum dots (QDs)/Cys-AuPt heterogeneous nanorings (NRs), serve as both a highly effective coreaction accelerator and the luminophore in a label-free ECL aptasensor. The novel AuPt nanodonuts were formed by decorating SnS2 QDs onto AuPt NR surfaces, which would promote the production of more coreactant intermediate in the SnS2 QDs/K2S2O8 system. As a result, the ECL performance was greatly improved. Meanwhile, l-cysteine (l-Cys) played an important role in the combination between AuPt NRs and SnS2 QDs, and the nanodonuts served as the matrix to load numerous lincomycin (Lin) aptamers. Under optimal conditions, the ECL aptasensor exhibited ultrasensitive detection of Lin from 1 fg/mL to 0.1 pg/mL with a limit of detection (LOD) of 0.7 fg/mL (1.72 fM).
摘要：
PURPOSE: To explore the clinical characteristics of Micrococcus luteus bloodstream infection in an infant and characterize the phenotype and genotype of the isolated strains, as well as seek suitable infection models for assessing virulence. METHODS: Clinical data was collected from an infant patient diagnosed with M. luteus bloodstream infection. Metagenomic sequencing was performed on the isolated blood sample. The strain was isolated and underwent mass spectrometry, biochemical tests, antibiotic susceptibility assays, and whole-genome sequencing. The Galleria mellonella infection model was used to assess M. luteus virulence. RESULTS: Patient responded poorly to cephalosporins, but recovered after Linezolid treatment. Metagenomic sequencing identified M. luteus as the predominant species in the sample, confirming infection. They were identified as M. luteus with a high confidence level of 98.99% using mass spectrometry. The strain showed positive results for Catalase, Oxidase, and Urea tests, and negative results for Mannose, Xylose, Lactose, Mannitol, Arginine, and Galactose tests, consistent with the biochemical profile of M. luteus reference standards. M. luteus susceptibility to 15 antibiotics was demonstrated and no resistance genes were detected. Predicted virulence genes, including clpB, were associated with metabolic pathways and the type VI secretion system. The infection model demonstrated dose-dependent survival rates. CONCLUSION: The infant likely developed a bloodstream infection with M. luteus due to compromised immunity. Although the isolated strain is sensitive to cephalosporin antibiotics and has low pathogenicity in infection models, clinical treatment with cephalosporins was ineffective. Linezolid proved to be effective, providing valuable guidance for future clinical management of such rare infections.
作者机构：
[Zheng, Xingyu; Qu, Xiaowang; He, Rongzhang; Liu, Wenpei] Univ South China, Hengyang Med Sch, Coll Basic Med Sci, Hengyang 421001, Peoples R China.;[Zheng, Xingyu; Qu, Xiaowang; He, Rongzhang; Liu, Wenpei] MOE Key Lab Rare Pediat Dis, Hengyang 421001, Peoples R China.;[Zheng, Xingyu; Zhang, Jian; Wang, You; Pan, Dong; Liu, Ziyan; Liu, Bo; Lu, Rui; Chen, Jun; Wu, Qian; Qu, Xiaowang; Teng, Shishan; Peng, Liting; He, Rongzhang; Hu, Yabin; Yang, Jing; Liu, Wenpei] Univ South China, Translat Med Inst, Peoples Hosp Chenzhou 1, Chenzhou 423000, Peoples R China.;[Xie, Ting; Wang, Qijie] Cent Hosp Shaoyang, Shaoyang 422000, Peoples R China.;[Liu, Yongchen; Li, Yi-Ping; Chang, Fangfang; Wu, Qian; Li, YP] Sun Yat Sen Univ, Inst Human Virol, Zhongshan Sch Med, Guangzhou 501180, Peoples R China.
通讯机构：
[Qu, XW ] U;[Li, YP ] S;[Wang, YC ] N;Univ South China, Hengyang Med Sch, Coll Basic Med Sci, Hengyang 421001, Peoples R China.;MOE Key Lab Rare Pediat Dis, Hengyang 421001, Peoples R China.
摘要：
Long-term humoral immunity to SARS-CoV-2 is essential for preventing reinfection. The production of neutralizing antibody (nAb) and B cell differentiation are tightly regulated by T follicular help (T(FH)) cells. However, the longevity and functional role of T(FH) cell subsets in COVID-19 convalescents and vaccine recipients remain poorly defined. Here, we show that SARS-CoV-2 infection and inactivated vaccine elicited both spike-specific CXCR3(+) T(FH) cell and CXCR3(-) T(FH) cell responses, which showed distinct response patterns. Spike-specific CXCR3(+) T(FH) cells exhibit a dominant and more durable response than CXCR3(-) T(FH) cells that positively correlated with antibody responses. A third booster dose preferentially expands the spike-specific CXCR3(+) T(FH) cell subset induced by two doses of inactivated vaccine, contributing to antibody maturation and potency. Functionally, spike-specific CXCR3(+) T(FH) cells have a greater ability to induce spike-specific antibody secreting cells (ASCs) differentiation compared to spike-specific CXCR3(-) T(FH) cells. In conclusion, the persistent and functional role of spike-specific CXCR3(+) T(FH) cells following SARS-CoV-2 infection and vaccination may play an important role in antibody maintenance and recall response, thereby conferring long-term protection. The findings from this study will inform the development of SARS-CoV-2 vaccines aiming to induce long-term protective immune memory.
摘要：
Herein, an ultrasensitive DNAzyme-based fluorescence biosensor for detecting Cu2+ was designed using the cascade signal amplification strategy, coupling lambda-exonuclease-assisted target recycling and mismatched catalytic hairpin assembly (MCHA). In the designed detection system, the target, Cu2+, can activate the Cu2+-dependent DNAzyme to cause a cleavage reaction, releasing ssDNA (tDNA). Then, tDNA binds to hairpin DNA (H0) with an overhanging 5 '-phosphorylated terminus to form dsDNA with a blunt 5 '-phosphorylated terminus, which activates the dsDNA to be digested by lambda-Exo and releases tDNA along with another ssDNA (iDNA). Subsequently, the iDNA initiates MCHA, which can restore the fluorescence of carboxyfluorescein (FAM) previously quenched by tetramethylrhodamine (TAMRA), resulting in a strong fluorescent signal. Furthermore, MCHA efficiently improves the signal-to-noise ratio of the detection system. More importantly, tDNA recycling can be achieved with the lambda-Exo digestion reaction to release more iDNA, efficiently amplifying the fluorescent signal and further improving the sensitivity to Cu2+ with a detection limit of 60 fM. The practical application of the developed biosensor was also demonstrated by detecting Cu2+ in real samples, proving it to be an excellent analytical strategy for the ultrasensitive quantification of heavy metal ions in environmental water sources.
作者机构：
[Wu, Yuxiang; Chen, Lin; Xu, Guodong; Ru, Qin] Jianghan Univ, Dept Hlth & Phys Educ, Wuhan 430056, Peoples R China.;[Xie, Wenqing; Ding, Yilan; Li, Yusheng] Cent South Univ, Xiangya Hosp, Dept Orthoped, Changsha 410008, Peoples R China.;[Xie, Wenqing; Ding, Yilan; Li, Yusheng] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Peoples R China.;[Wang, Fudi] Zhejiang Univ, Affiliated Hosp 2, Sch Publ Hlth, Sch Med,State Key Lab Expt Hematol, Hangzhou, Peoples R China.;[Wang, Fudi] Univ South China, Affiliated Hosp 1, Sch Publ Hlth, Hengyang Med Sch,Basic Med Sci, Hengyang, Peoples R China.
通讯机构：
[Wu, Yuxiang] D;[Wang, Fudi] T;The Second Affiliated Hospital, School of Public Health, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou, China<&wdkj&>The First Affiliated Hospital, Basic Medical Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China<&wdkj&>Department of Health and Physical Education, Jianghan University, Wuhan, China
关键词：
METABOLISM;DISEASES;PEROXIDATION
摘要：
Ferroptosis, a unique type of cell death, is characterized by iron-dependent accumulation and lipid peroxidation. It is closely related to multiple biological processes, including iron metabolism, polyunsaturated fatty acid metabolism, and the biosynthesis of compounds with antioxidant activities, including glutathione. In the past 10 years, increasing evidence has indicated a potentially strong relationship between ferroptosis and the onset and progression of age-related orthopedic diseases, such as osteoporosis and osteoarthritis. Therefore, in-depth knowledge of the regulatory mechanisms of ferroptosis in age-related orthopedic diseases may help improve disease treatment and prevention. This review provides an overview of recent research on ferroptosis and its influences on bone and cartilage homeostasis. It begins with a brief overview of systemic iron metabolism and ferroptosis, particularly the potential mechanisms of ferroptosis. It presents a discussion on the role of ferroptosis in age-related orthopedic diseases, including promotion of bone loss and cartilage degradation and the inhibition of osteogenesis. Finally, it focuses on the future of targeting ferroptosis to treat age-related orthopedic diseases with the intention of inspiring further clinical research and the development of therapeutic strategies.
