Insect Science
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2025
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IF 3
Junna Liu,Zhaoyang Li,Zexin Zhong,Jianxing Li,Qi Chen,Ran Gao,Xuguo Zhou,Youjun Zhang,Chunxiao Yang,Huipeng Pan
LIM-HD (homeodomain) protein is essential for the specific differentiation of various cells and tissues due to its conserved HD. Within the LIM subclass, the LIM-HD transcription factor 1 alpha ( Lmx1a ) remains poorly characterized in insects. This study investigates the expression patterns of HvLmx1a in the 28-spotted lady beetle, Henosepilachna vigintioctopunctata , at both developmental stage and tissue levels. Furthermore, RNA interference (RNAi)-mediated knockdown of HvLmx1a resulted in increased mortality during the early larval stage. Injection of ds HvLmx1a at the beginning of the 4th instar caused a reduction in 20E titer, disrupted normal molting and pupation processes, and led to the emergence of larval-pupal abnormalities. Notably, HvLmx1a expression was significantly down-regulated on d 2 and 4 post-injection, which coincided with a marked inhibition of HvCHS1 and genes associated with 20E and bursicon signaling pathways. Additionally, silencing HvLmx1a induced qualitative changes in male testes and female ovaries, resulting in infertility and increased mortality. Ultimately, these findings suggest that HvLmx1a influences ovarian morphology and development through lipid metabolism. In conclusion, this study provides the first evidence of the diverse physiological roles of Lmx1a in H. vigintioctopunctata and highlight its potential as a target for RNAi-based biological control strategies.
研究领域:
昆虫学
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分子生物学
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发育生物学
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PubMed
高影响因子
ANALYTICAL CHEMISTRY
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2018
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IF 6.042
Xun Liu,Shang-Qing Zhang,Zi-Han Cheng,Xing Wei,Ting Yang,Yong-Liang Yu,Ming-Li Chen,Jian-Hua Wang
A highly sensitive platform is developed for the determination of microRNA-21 (miRNA-21) with inductively coupled plasma mass spectrometry (ICPMS). It includes the following operations: Hairpin structures DNA H1 and H2 are designed, and DNA H1 is bound to ultrasmall lanthanide upconversion nanoparticles (UCNPs) to produce UCNPs@DNA conjugate probes. Target miRNA triggers a chain reaction for alternating hybridization between DNA H1 (bound on UCNPs@DNA probe) and DNA H2. This leads to UCNPs accumulation and serves as an efficient amplification strategy for UCNPs. The concentration of miRNA-21 is closely correlated to the number of UCNPs; thus, the detection of 89Y by ICPMS provides a promising approach for miRNA quantification. This protocol exhibits high sensitivity to miRNA-21 within 0.1–500 fM, along with a detection limit of 41 aM, which is among the hitherto reported most sensitive procedures. It is worth mentioning that rare earth elements are scarcely present in living systems, which minimizes the background for ICPMS detection and excludes potential interferences from the coexisting species, which is most suited for biological assay.
研究领域:
生物化学
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分析化学
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分子生物学
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PubMed
高影响因子
Acta Biomaterialia
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2025
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IF 9.6
Chunfa Chen,Quan Li,Beinuo Wang,Qian Liu,Zi Wang,Bihang Zhang,Lu Wang,Yujuan Zou,Ziye Mou,Chengshan Ren,Zaichun You,Bin Wang,Zhi Xu,Hang Qian
Acute lung injury (ALI) is characterized by widespread inflammation and oxidative stress, leading to impaired gas exchange and significant morbidity. In this study, we propose a potential approach using a magnesium-free DNA self-assembly strategy to assemble a DNA nanotube that carries agmatine and microRNA-126b mimics (NT AGM -126). Agmatine not only reduces electrostatic repulsion between DNA helices, thereby facilitating the folding of the DNA nanotube, but also serves as a drug that inhibits iNOS signaling. The microRNA-126b mimics restore the downregulated microRNA-126b in macrophages and suppress inflammation by targeting high mobility group box 1 (HMGB1). Preliminary results indicated that agmatine can effectively facilitate the assembly of the DNA nanotube, improve serum stability, and enhance the cellular uptake efficiency of NT AGM -126. Further in vitro and in vivo results demonstrate that NT AGM -126 effectively reduces oxidative stress and inflammation by downregulating iNOS and HMGB1, providing a combined therapeutic effect in ALI. This study highlights the potential of agmatine-facilitated DNA nanostructures as a versatile drug delivery platform for treating inflammatory diseases, broadening the application of DNA nanotechnology in biomedical research. Statement of Significance This study introduces a promising therapeutic approach using a magnesium-free DNA self-assembly strategy to create a DNA nanotube (NT AGM -126) that carries agmatine and microRNA-126b mimics. The agmatine not only aids in the assembly and stability of the DNA nanotube but also inhibits iNOS signaling, while the microRNA-126b mimics restore downregulated microRNA-126b in macrophages and suppress inflammation by targeting HMGB1. Preliminary and further results demonstrate that NT AGM -126 effectively reduces oxidative stress and inflammation, providing a synergistic therapeutic effect in ALI. This study underscores the potential of agmatine-facilitated DNA nanostructures as a versatile drug delivery platform, broadening the application of DNA nanotechnology in the treatment of inflammatory diseases and advancing biomedical research.
研究领域:
生物医学工程
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分子生物学
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药学
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PubMed
高影响因子
Cell Communication and Signaling
·
2025
·Vol. 23
·期 1
·1-17
·
IF 8.9
Xu Teng,Wang Yaning,Zhao Zechen,Wang Jinsong,Zhao Zhenyuan,Yang Yuemei,Song Xiaomeng,Lai Qingguo
Background Tumor dissemination is a life-threatening event which confers to most cancer-related deaths with limited effective therapeutic option. TNFα-induced protein 2 (TNFAIP2) reveals pro-metastasis potential in several cancers. However, its definite role and underlying mechanism in oral squamous cell carcinoma (OSCC) is largely unknown. Methods The impact of TNFAIP2 on tumor metastasis was assessed based on the conditional knockout mouse with 4-nitroquinoline-1-oxide (4NQO) induced OSCC model through feature and immunohistochemistry analysis. To explore the specific mechanism, enrichment analysis and co-immunoprecipitation were applied. Meanwhile, the nano-hydroxyapatite (nHAp) and poly-L-lysine (PLL) based RNA interference delivery system was designed to restrict tumor dissemination. Results The conditional knockout Tnfaip2 in epithelium reduced tumor initiation rate, differentiation degree and cervical lymph node metastasis (LNM) in mouse exposed to 4NQO. Enrichment analysis suggested nuclear factor-kappa B (NF-κB) signaling was associated with these effects. Western blot proved that TNFAIP2 prevented the ubiquitin proteasome degradation of inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta (IKKβ), a classical transcriptional activator protein in NF-κB signaling. Mechanistically, TNFAIP2 was demonstrated to competitively interact with kelch-like ECH-associated protein 1 (KEAP1) to avoid IKKβ from ubiquitination at K63 and proteasomal degradation subsequently, which finally sustained NF-κB signaling and facilitated tumor metastasis by enhancing epithelial-mesenchymal transition (EMT) and lymphangiogenesis. Notably, the synthetic small interfering RNA delivery systems nHAp@PLL-siTnfaip2 showed significant effect in attenuating tumor progression of OSCC mouse. Conclusion Above results showed TNFAIP2 promoted EMT and lymphangiogenesis of OSCC by regulating NF-κB signaling, a mechanism that was dependent on the interaction with KEAP1 competitively. The nHAp based TNFAIP2 interference might serve as a novel therapeutic in limiting OSCC metastasis.
研究领域:
肿瘤学
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分子生物学
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口腔医学
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生物化学
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PubMed
高影响因子
MOLECULAR THERAPY
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2025
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IF 12
Jingjing Zhang,Chao Li,Yuheng Liu,Rui Liao,Dian He,Lifeng Xu,Tingting Chen,Qin Xiao,Mingxing Luo,Yang Chen,Yali Li,Huaxing Zhu,Joseph Rosenecker,Xiaoyan Ding,Shuchen Pei,Shan Guan
The development of mucosal mRNA vaccines is promising but extremely challenging. Major efforts have been focused on optimizing delivery systems, whereas it is still unknown whether the intrinsic quality of mRNA components significantly impacts the potency of airway inoculated mRNA vaccines. Here, we systematically demonstrate mucosal mRNA vaccine requires higher standards of purification and tailor-designed sequence to fulfil its potency compared to parenteral-route inoculated counterpart. Double-stranded RNA (dsRNA) contaminants are prone to trigger innate immune response in the airway that activates the mRNA degradation mechanism, thereby diminishing the mRNA expression and subsequent antigen-specific immune responses. To address these challenges, we developed a strategy that combines optimized untranslated regions (UTRs) screened from endogenous genes of pulmonary cells with affinity chromatography-based purification which effectively removed dsRNA contaminants. The optimized mRNA administered via airway route not only demonstrated superior protein expression (30-fold increase) and reduced inflammation in the lung, but also promoted robust immunity comprising significantly elevated systemic, cellular, and mucosal immune responses, which was in stark contrast to intramuscular injected counterpart that displays less pronounced benefits. Our findings offer new insights into the development of mucosal mRNA therapeutics from an overlooked but crucial perspective of optimizing mRNA components.
研究领域:
免疫学
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分子生物学
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疫苗开发
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PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2025
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IF 7.7
Mengyi Tian,Youqiang Xing,Wei Wang,Ze Wu,Peng Huang,Bingjue Li,Lei Liu
Accurate detection of microRNA concentrations is essential for early cancer diagnosis and monitoring. Existing methods typically provide a linear response within a limited concentration range, which hinders their precise clinical application. This study presents a novel sensing approach using the fluorescence properties of nitrogen vacancy (NV) centers. Magnetic particles capture and enrich fluorescent nanodiamonds (FNDs), and effectively address signal inconsistencies due to variations in FND particles by applying a voltage that regulates the NV center fluorescence. Our method achieves a linear response to microRNAs across a broad concentration range (10 fM to 1 μM), with the determination coefficient (R²) of the fluorescence signal, enhanced from 0.8711 to 0.9951 through voltage modulation. Additionally, optimizing experimental conditions and enhancing FND fluorescence increased the signal intensity, achieving a minimum detection limit of 7.17 fM. The combination of sensitive detection and an extensive linear range suggests the potential of this strategy as a universal detection method for the early diagnosis of various diseases.
研究领域:
生物医学工程
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分子生物学
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量子传感
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高影响因子
Autophagy
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2018
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IF 11.1
Bing Han,Yuan Zhang,Yanhong Zhang,Ying Bai,Xufeng Chen,Rongrong Huang,Fangfang Wu,Shuo Leng,Jie Chao,John H. Zhang,Gang Hu,Honghong Yao
Circular RNAs (circRNAs) are highly expressed in the central nervous system and are involved in the regulation of physiological and pathophysiological processes. However, the potential role of circRNAs in stroke remains largely unknown. Here, using a circRNA microarray, we showed that circular RNA Hectd1 (circHectd1) levels were significantly increased in ischemic brain tissues in transient middle cerebral artery occlusion (tMCAO) mouse stroke models and further validated this finding in plasma samples from acute ischemic stroke (AIS) patients. Knockdown of circHectd1 expression significantly decreased infarct areas, attenuated neuronal deficits, and ameliorated astrocyte activation in tMCAO mice. Mechanistically, circHECTD1 functions as an endogenous MIR142 (microRNA 142) sponge to inhibit MIR142 activity, resulting in the inhibition of TIPARP (TCDD inducible poly[ADP-ribose] polymerase) expression with subsequent inhibition of astrocyte activation via macroautophagy/autophagy. Taken together, the results of our study indicate that circHECTD1 and its coupling mechanism are involved in cerebral ischemia, thus providing translational evidence that circHECTD1 can serve as a novel biomarker of and therapeutic target for stroke.Abbreviations: 3-MA: 3-methyladenine; ACTB: actin beta; AIS: acute ischemic stroke; AS: primary mouse astrocytes; BECN1: beclin 1, autophagy related; BMI: body mass index; circHECTD1: circRNA HECTD1; circRNAs: circular RNAs; CBF: cerebral blood flow; Con: control; DAPI: 4ʹ,6-diamidino-2-phenylindole; ECA: external carotid artery; FISH: fluorescence in situ hybridization; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; Gdna: genomic DNA; GFAP: glial fibrillary acidic protein; GO: gene ontology; HDL: high-density lipoprotein; IOD: integrated optical density; LDL: low-density lipoprotein; LPA: lipoprotein(a); MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MIR142: microRNA 142; mNSS: modified neurological severity scores; MRI: magnetic resonance imaging; NIHSS: National Institute of Health Stoke Scale; OGD-R: oxygen glucose deprivation-reperfusion; PCR: polymerase chain reaction; PFA: paraformaldehyde; SQSTM1: sequestosome 1; TIPARP: TCDD inducible poly(ADP-ribose) polymerase; tMCAO: transient middle cerebral artery occlusion; TTC: 2,3,5-triphenyltetrazolium chloride; UTR: untranslated region; WT: wild type
研究领域:
神经科学
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分子生物学
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中风研究
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基因调控
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PubMed
高影响因子
Nature Communications
·
2025
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IF 15.7
Qianqian Ying,Yongchen Chen,Luochen Shen,Yang Xu,Ruilin Tian
RNA splicing is fundamental to cellular function, yet systematic investigation of its complex regulation has been limited by existing methods. Here, we present SPLiCR-seq ( SPL icing regulator i dentification through CR ISPR screening), a high-throughput CRISPR screening platform that enables direct measurement of RNA splicing outcomes for pooled genetic perturbations, overcoming limitations of traditional fluorescence-based approaches. Applying SPLiCR-seq to investigate XBP1 splicing during the unfolded protein response (UPR), we conduct targeted and genome-wide screens across diverse cellular contexts, revealing both common and cell-type specific regulators. Notably, we identify GADD34 ( PPP1R15A ) as a novel modulator of IRE1α-XBP1 signaling, demonstrating that it directly interacts with IRE1α and functions independently of its canonical role in eIF2α dephosphorylation. Pharmacological inhibition of GADD34 using Sephin1 effectively suppressed XBP1 splicing and alleviated CAR-T cell exhaustion in an ex vivo model, leading to enhanced tumor-killing capacity across multiple cancer models. This work not only establishes a powerful new tool for systematically studying RNA splicing regulation but also uncovers a promising therapeutic strategy for improving CAR-T cell immunotherapy through modulation of the IRE1α-XBP1 pathway. Systematic investigation of RNA splicing regulation remains challenging. Here, authors present SPLiCR-seq, a CRISPR platform enabling direct measurement of splicing outcomes for pooled perturbations. They identify GADD34 as a novel IRE1α-XBP1 regulator, with inhibition enhancing CAR-T cell activity.
研究领域:
分子生物学
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遗传学
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RNA生物学
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免疫治疗
·
细胞信号转导
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CRISPR技术
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癌症研究
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DOI
PubMed
高影响因子
Cell and Bioscience
·
2025
·Vol. 15
·期 1
·159
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IF 6.2
Sun Weikang,Zhang Mengyu,Wang Ruilin,Yang Jie,Rasool Ameena Tur,Luo Renjie,Liu Xiangdong,Cao Peng,Li Erguang
Background The RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1), also known as heterogeneous nuclear ribonucleoprotein I (hnRNP I), mediates gene expression through splicing regulation. Its role in virus infection is undefined. Results We show that genetic ablation of PTBP1 renders cell resistant to herpes simplex virus 1 (HSV-1) infection. HSV-1 utilizes 3-O-sulfated heparan sulfate proteoglycans (HSPGs) for attachment and for infection of epithelial cells. We found that knockout of PTBP1 expression resulted in loss of HS3ST3A1 and HS3ST3B1, heparan sulfate glucosaminyl 3-O-sulfotransferase genes for 3-O-sulfation of the heparan sulfate (HS) chains of HSPGs. Each of the HS3ST3A1/HS3ST3B1 genes is composed of 2 exons separated by an extraordinarily long intron whose removal requires PTBP1-associated looping. We found that PTBP1 interacted with the intronic region of HS3ST3A1/HS3ST3B1 pre-mRNAs and modulated their processing to mRNA. The essential role of PTBP1 in functional HS3ST3A1 expression and in HSV-1 infection was demonstrated by ectopic re-expression in the knockout (ko) cells. In addition, we showed that targeting PTBP1 expression by microRNA mimics reduced disease symptoms in a mouse herpetic stromal keratitis (HSK) model. Conclusions The results demonstrate that PTBP1 mediates HSV-1 infection of epithelial cells through splicing regulation of HS3ST3A1/HS3ST3B1. These studies provide a new area for novel therapeutic strategies through splicing regulation. Graphical abstract By Sun et al. RNA-binding protein PTBP1 mediates HSV-1 attachment and infection through regulation of heparan sulfate 3-O-sulfotransferase gene expression.
研究领域:
分子生物学
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病毒学
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细胞生物学
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基因表达调控
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RNA剪接
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感染免疫
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眼科学
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转化医学
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产品关联
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PubMed
高影响因子
TALANTA
·
2023
·
IF 6.1
Haodong Cui,Wenxing Song,Xiaoling Ru,Wen Fu,Ling Ji,Wenhua Zhou,Zhen Zhao,Guangbo Qu,Xue-Feng Yu,Guibin Jiang
The ongoing outbreak of the novel coronavirus disease 2019 (COVID-19) draws worldwide concerns due to its long incubation period and strong infectivity. Although RT-PCR-based methods are being widely applied for clinical diagnosis, timely and accurate diagnosis towards COVID-19 causing virus, the SARS-CoV-2, is still limited due to labor-intensive and time-consuming operations. Herein, we report a new viral RNA extraction method based on poly-(amino ester) with carboxyl group (PC)-coated magnetic nanoparticles (pcMNPs) for the sensitive detection of SARS-CoV-2. This method combines the lysis and binding steps into one step, and refines multiple washing steps into one step, giving a turnaround time of less than 9 min. Furthermore, the extracted pcMNP-RNA complexes can be directly introduced into subsequent RT-PCR reactions without elution. This simplified viral RNA method could be well adapted in fast manual and automated high-throughput nucleic acids extraction protocols suitable for different scenarios. A high sensitivity down to 100 copies/mL and a linear correlation between 100 and 10 6 copies/mL of SARS-CoV-2 pseudovirus particles are achieved in both protocols. Benefitting from the simplicity and excellent performances, this new method can dramatically improve the efficiency and reduce operational requirements for the early clinical diagnosis and large-scale SARS-CoV-2 nucleic acid screening.
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高影响因子
BIOSENSORS & BIOELECTRONICS
·
2022
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IF 12.545
Yang Sun,Cheng Yang,Xiaolin Jiang,Pengbo Zhang,Shuo Chen,Fengxia Su,Hui Wang,Weiliang Liu,Xiaofei He,Lei Chen,Baoyuan Man,Zhengping Li
False detection of SARS-CoV-2 is detrimental to epidemic prevention and control. The scalar nature of the detected signal and the imperfect target recognition property of developed methods are the root causes of generating false signals. Here, we reported a collaborative system of CRISPR-Cas13a coupling with the stabilized graphene field-effect transistor, providing high-intensity vector signals for detecting SARS-CoV-2. In this collaborative system, SARS-CoV-2 RNA generates a “big subtraction” signal with a right-shifted feature, whereas any untargets cause the left-shifted characteristic signal. Thus, the false detection of SARS-CoV-2 is eliminated. High sensitivity with 0.15 copies/μL was obtained. In addition, the wide concerned instability of the graphene field-effect transistor for biosensing in solution environment was solved by the hydrophobic treatment to its substrate, which should be a milestone in advancing it's engineering application. This collaborative system characterized by the high-intensity vector signal and amazing stability significantly advances the accurate SARS-CoV-2 detection from the aspect of signal nature.
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高影响因子
CELLULAR SIGNALLING
·
2023
·
IF 4.8
Sijia Han,Xueying Jin,Tianyu Hu,Feng Chi
Non-SMC condensin II complex subunit G2 (NCAPG2) is one of the three non-SMC subunits in condensin II, which plays a vital role in regulating chromosome condensation and segregation. Although the tumor-promoting role of NCAPG2 has been reported in several solid malignancies, its function in breast invasive carcinoma (BRCA) remains unknown. Data both from GEPIA and GSE36295 indicated that NCAPG2 mRNA expression was abnormally upregulated in cancer tissues, which was further verified in 40 paired BRCA and para-carcinoma samples. Kaplan-Meier Plotter further illustrated that BRCA patients with higher NCAPG2 expression have a poorer prognosis. Functional experiments carried out in two BRCA cell lines (MCF-7 and T-47D) showed that NCAPG2-silenced BRCA cells acquired less aggressive behavior — weakened growth and metastasis both in vitro and in vivo. Label-free proteomics quantified the protein expression patterns in MCF-7 cells, and the results revealed 684 differentially expressed proteins (|log 2 FC| > 1 and P < 0.05) downstream to NCAPG2. Interestingly, poly(C)-binding protein 2 (PCBP2), an RNA binding protein previously known to increase RNA stability of its target genes, was found to directly bind to and protect NCAPG2 mRNA from degradation—PCBP2 knockdown accelerated the degradation half-life time of NCAPG2 mRNA from approximately 8 h to 5 h. Taken together, our study indicates that NCAPG2 acts as a novel contributor to BRCA growth and metastasis under the regulation of PCBP2, providing insights into BRCA treatment.
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高影响因子
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