Standard: human intestine-on-a-chip.

Organs-on-chips are microphysiological systems that allow to replicate the key functions of human organs and accelerate the innovation in life sciences including disease modeling, drug development, and precision medicine. However, due to the lack of standards in their definition, structural design, cell source, model construction, and functional validation, a wide range of translational application of organs-on-chips remains a challenging. "Organs-on-chips: Intestine" is the first group standard on human intestine-on-a-chip in China, jointly agreed and released by the experts from the Chinese Society of Biotechnology on 29th April 2024. This standard specifies the scope, terminology, definitions, technical requirements, detection methods, and quality control in building the human intestinal model on a chip. The publication of this group standard will guide the institutional establishment, acceptance and execution of proper practical protocols and accelerate the international standardization of intestine-on-a-chip for translational applications.

Low-dose ionizing radiation-induced RET/PTC1 rearrangement via the non-homologous end joining pathway to drive thyroid cancer.

Thyroid cancer incidence increases worldwide annually, primarily due to factors such as ionizing radiation (IR), iodine intake, and genetics. Papillary carcinoma of the thyroid (PTC) accounts for about 80% of thyroid cancer cases. RET/PTC1 (coiled-coil domain containing 6 [CCDC6]-rearranged during transfection) rearrangement is a distinctive feature in over 70% of thyroid cancers who exposed to low doses of IR in Chernobyl and Hiroshima‒Nagasaki atomic bombings. This study aims to elucidate mechanism between RET/PTC1 rearrangement and IR in PTC. N-thy-ori-3-1 cells were subjected to varying doses of IR (2/1/0.5/0.2/0.1/0.05 Gy) of IR at different days, and result showed low-dose IR-induced RET/PTC1 rearrangement in a dose-dependent manner. RET/PTC1 has been observed to promote PTC both in vivo and in vitro. To delineate the role of different DNA repair pathways, SCR7, RI-1, and Olaparib were employed to inhibit non-homologous end joining (NHEJ), homologous recombination (HR), and microhomology-mediated end joining (MMEJ), respectively. Notably, inhibiting NHEJ enhanced HR repair efficiency and reduced IR-induced RET/PTC1 rearrangement. Conversely, inhibiting HR increased NHEJ repair efficiency and subsequent RET/PTC1 rearrangement. The MMEJ did not show a markable role in this progress. Additionally, inhibiting DNA-dependent protein kinase catalytic subunit (DNA-PKcs) decreased the efficiency of NHEJ and thus reduced IR-induced RET/PTC1 rearrangement. To conclude, the data suggest that NHEJ, rather than HR or MMEJ, is the critical cause of IR-induced RET/PTC1 rearrangement. Targeting DNA-PKcs to inhibit the NHEJ has emerged as a promising therapeutic strategy for addressing IR-induced RET/PTC1 rearrangement in PTC.

TNKS1BP1 mediates AECII senescence and radiation induced lung injury through suppressing EEF2 degradation.

BACKGROUND: Although recent studies provide mechanistic understanding to the pathogenesis of radiation induced lung injury (RILI), rare therapeutics show definitive promise for treating this disease. Type II alveolar epithelial cells (AECII) injury in various manner results in an inflammation response to initiate RILI. RESULTS: Here, we reported that radiation (IR) up-regulated the TNKS1BP1, causing progressive accumulation of the cellular senescence by up-regulating EEF2 in AECII and lung tissue of RILI mice. Senescent AECII induced Senescence-Associated Secretory Phenotype (SASP), consequently activating fibroblasts and macrophages to promote RILI development. In response to IR, elevated TNKS1BP1 interacted with and decreased CNOT4 to suppress EEF2 degradation. Ectopic expression of EEF2 accelerated AECII senescence. Using a model system of TNKS1BP1 knockout (KO) mice, we demonstrated that TNKS1BP1 KO prevents IR-induced lung tissue senescence and RILI. CONCLUSIONS: Notably, this study suggested that a regulatory mechanism of the TNKS1BP1/CNOT4/EEF2 axis in AECII senescence may be a potential strategy for RILI.

Protein lysine crotonylation in cellular processions and disease associations.

Protein lysine crotonylation (Kcr) is one conserved form of posttranslational modifications of proteins, which plays an important role in a series of cellular physiological and pathological processes. Lysine ε-amino groups are the primary sites of such modification, resulting in four-carbon planar lysine crotonylation that is structurally and functionally distinct from the acetylation of these residues. High levels of Kcr modifications have been identified on both histone and non-histone proteins. The present review offers an update on the research progression regarding protein Kcr modifications in biomedical contexts and provides a discussion of the mechanisms whereby Kcr modification governs a range of biological processes. In addition, given the importance of protein Kcr modification in disease onset and progression, the potential viability of Kcr regulators as therapeutic targets is elucidated.

Voltage-dependent anion channel 1 mediates mitochondrial fission and glucose metabolic reprogramming in response to ionizing radiation.

The ionizing radiation (IR) represents a formidable challenge as an environmental factor to mitochondria, leading to disrupt cellular energy metabolism and posing health risks. Although the deleterious impacts of IR on mitochondrial function are recognized, the specific molecular targets remain incompletely elucidated. In this study, HeLa cells subjected to γ-rays exhibited concomitant oxidative stress, mitochondrial structural alterations, and diminished ATP production capacity. The γ-rays induced a dose-dependent induction of mitochondrial fission, simultaneously manifested by an elevated S616/S637 phosphorylation ratio of the dynamin-related protein 1 (DRP1) and a reduction in the expression of the mitochondrial fusion protein mitofusin 2 (MFN2). Knockdown of DRP1 effectively mitigated γ-rays-induced mitochondrial network damage, implying that DRP1 phosphorylation may act as an effector of radiation-induced mitochondrial damage. The mitochondrial outer membrane protein voltage-dependent anion channel 1 (VDAC1) was identified as a crucial player in IR-induced mitochondrial damage. The VDAC1 inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), counteracts the excessive mitochondrial fission induced by γ-rays, consequently rebalancing the glycolytic and oxidative phosphorylation equilibrium. This metabolic shift was uncovered to enhance glycolytic capacity, thus fortifying cellular resilience and elevating the radiosensitivity of cancer cells. These findings elucidate the intricate regulatory mechanisms governing mitochondrial morphology under radiation response. It is anticipated that the development of targeted drugs directed against VDAC1 may hold promise in augmenting the sensitivity of tumor cells to radiotherapy and chemotherapy.

Decrotonylation of cGAS K254 prompts homologous recombination repair by blocking its DNA binding and releasing PARP1.

Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor, also exhibits nuclear genomic localization and is involved in DNA damage signaling. In this study, we investigated the impact of cGAS crotonylation on the regulation of the DNA damage response, particularly homologous recombination repair, following exposure to ionizing radiation (IR). Lysine 254 of cGAS is constitutively crotonylated by the CREB-binding protein; however, IR-induced DNA damage triggers sirtuin 3 (SIRT3)-mediated decrotonylation. Lysine 254 decrotonylation decreased the DNA-binding affinity of cGAS and inhibited its interaction with PARP1, promoting homologous recombination repair. Moreover, SIRT3 suppression led to homologous recombination repair inhibition and markedly sensitized cancer cells to IR and DNA-damaging chemicals, highlighting SIRT3 as a potential target for cancer therapy. Overall, this study revealed the crucial role of cGAS crotonylation in the DNA damage response. Furthermore, we propose that modulating cGAS and SIRT3 activities could be potential strategies for cancer therapy.

Low-dose radiation promotes high-fat diet-induced atherosclerosis by activating cGAS signal pathway.

BACKGROUND: Atherosclerosis (AS) is the most prevalent cardiovascular disease, with an exceptionally high burden. High-fat diet (HFD) is a popular diet behavior, whereas low-dose radiation (LDR) is an environmental physical factor. There is evidence to suggest that an HFD may exacerbate the onset of atherosclerosis. Whether the combination effect of HFD and LDR would have potential on atherosclerosis development remains incompletely unclear. METHODS: In this study, ApoE-/- mice were used as atherosclerosis model animals to investigate the combination effects of HFD and LDR (10 × 0.01Gy, or 20 × 0.01Gy) on vascular lesions. Doppler ultrasound imaging, H&E staining, oil red O staining, western blotting, and immunohistochemistry (IHC) were used to assess the pro-atherosclerotic effects. LC-MS was used to detect the non-targeted lipidomic. RESULTS: Long-term exposure of low-dose radiation at an accumulated dose of 0.2Gy significantly increased the occurrence of vascular stiffness and the aortic lesion in ApoE-/- mice. The synergistic effect of HFD and LDR was observed in the development of atherosclerosis, which might be linked to both the dysbiosis of lipid metabolism and the stimulation of the inflammatory signaling system. Moreover, LDR but not HFD can activate the cGAS-STING signaling through increasing the yield of cytosolic mitochondrial DNAs as well as the expression of cGAS protein. The activation of cGAS-STING signal triggers the release of IFN-α/-ß, which functions as an inflammatory amplifier in the formation of atherosclerotic plaque. CONCLUSION: The current study offers fresh insights into the risks and mechanism that underlie the development of atherosclerosis by LDR, and there is a combination effect of LDR and HFD with the involvement of cGAS-STING signal pathway.

The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases.

The DNA-dependent protein kinase (DNA-PK), catalytic subunit, also known as DNA-PKcs, is complexed with the heterodimer Ku70/Ku80 to form DNA-PK holoenzyme, which is well recognized as initiator in the nonhomologous end joining (NHEJ) repair after double strand break (DSB). During NHEJ, DNA-PKcs is essential for both DNA end processing and end joining. Besides its classical function in DSB repair, DNA-PKcs also shows multifaceted functions in various biological activities such as class switch recombination (CSR) and variable (V) diversity (D) joining (J) recombination in B/T lymphocytes development, innate immunity through cGAS-STING pathway, transcription, alternative splicing, and so on, which are dependent on its function in NHEJ or not. Moreover, DNA-PKcs deficiency has been proven to be related with human diseases such as neurological pathogenesis, cancer, immunological disorder, and so on through different mechanisms. Therefore, it is imperative to summarize the latest findings about DNA-PKcs and diseases for better targeting DNA-PKcs, which have shown efficacy in cancer treatment in preclinical models. Here, we discuss the multifaceted roles of DNA-PKcs in human diseases, meanwhile, we discuss the progresses of DNA-PKcs inhibitors and their potential in clinical trials. The most updated review about DNA-PKcs will hopefully provide insights and ideas to understand DNA-PKcs associated diseases.

DNA-PKcs/AKT1 inhibits epithelial-mesenchymal transition during radiation-induced pulmonary fibrosis by inducing ubiquitination and degradation of Twist1.

INTRODUCTION: Radiation-induced pulmonary fibrosis (RIPF) is a chronic, progressive, irreversible lung interstitial disease that develops after radiotherapy. Although several previous studies have focused on the mechanism of epithelial-mesenchymal transition (EMT) in lung epithelial cells, the essential factors involved in this process remain poorly understood. The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) exhibits strong repair capacity when cells undergo radiation-induced damage; whether DNA-PKcs regulates EMT during RIPF remains unclear. OBJECTIVES: To investigate the role and molecular mechanism of DNA-PKcs in RIPF and provide an important theoretical basis for utilising DNA-PKcs-targeted drugs for preventing RIPF. METHODS: DNA-PKcs knockout (DPK-/-) mice were generated via the Cas9/sgRNA technique and subjected to whole chest ionizing radiation (IR) at a 20 Gy dose. Before whole chest IR, the mice were intragastrically administered the DNA-PKcs-targeted drug VND3207. Lung tissues were collected at 1 and 5 months after IR. RESULTS: The expression of DNA-PKcs is low in pulmonary fibrosis (PF) patients. DNA-PKcs deficiency significantly exacerbated RIPF by promoting EMT in lung epithelial cells. Mechanistically, DNA-PKcs deletion by shRNA or inhibitor NU7441 maintained the protein stability of Twist1. Furthermore, AKT1 mediated the interaction between DNA-PKcs and Twist1. High Twist1 expression and EMT-associated changes caused by DNA-PKcs deletion were blocked by insulin-like growth factor-1 (IGF-1), an AKT1 agonist. The radioprotective drug VND3207 prevented IR-induced EMT and alleviated RIPF in mice by stimulating the kinase activity of DNA-PKcs. CONCLUSION: Our study clarified the critical role and mechanism of DNA-PKcs in RIPF and showed that it could be a potential target for preventing RIPF.

GCN5 mediates DNA-PKcs crotonylation for DNA double-strand break repair and determining cancer radiosensitivity.

BACKGROUND: DNA double-strand break (DSB) induction and repair are important events for determining cell survival and the outcome of cancer radiotherapy. The DNA-dependent protein kinase (DNA-PK) complex functions at the apex of DSBs repair, and its assembly and activity are strictly regulated by post-translation modifications (PTMs)-associated interactions. However, the PTMs of the catalytic subunit DNA-PKcs and how they affect DNA-PKcs's functions are not fully understood. METHODS: Mass spectrometry analyses were performed to identify the crotonylation sites of DNA-PKcs in response to γ-ray irradiation. Co-immunoprecipitation (Co-IP), western blotting, in vitro crotonylation assays, laser microirradiation assays, in vitro DNA binding assays, in vitro DNA-PK assembly assays and IF assays were employed to confirm the crotonylation, identify the crotonylase and decrotonylase, and elucidate how crotonylation regulates the activity and function of DNA-PKcs. Subcutaneous xenografts of human HeLa GCN5 WT or HeLa GCN5 siRNA cells in BALB/c nude mice were generated and utilized to assess tumor proliferation in vivo after radiotherapy. RESULTS: Here, we reveal that K525 is an important site of DNA-PKcs for crotonylation, and whose level is sharply increased by irradiation. The histone acetyltransferase GCN5 functions as the crotonylase for K525-Kcr, while HDAC3 serves as its dedicated decrotonylase. K525 crotonylation enhances DNA binding activity of DNA-PKcs, and facilitates assembly of the DNA-PK complex. Furthermore, GCN5-mediated K525 crotonylation is indispensable for DNA-PKcs autophosphorylation and the repair of double-strand breaks in the NHEJ pathway. GCN5 suppression significantly sensitizes xenograft tumors of mice to radiotherapy. CONCLUSIONS: Our study defines K525 crotonylation of DNA-PKcs is important for the DNA-PK complex assembly and DSBs repair activity via NHEJ pathway. Targeting GCN5-mediated K525 Kcr of DNA-PKcs may be a promising therapeutic strategy for improving the outcome of cancer radiotherapy.

Exposure to polystyrene nanoplastics induces abnormal activation of innate immunity via the cGAS-STING pathway.

Endogenous immune defenses provide an intrinsic barrier against external entity invasion. Microplastics in the environment, especially those at the nanoscale (nanoplastics or NPs), may pose latent health risks through direct exposure. While links between nanoplastics and inflammatory processes have been established, detailed insights into how they may perturb the innate immune mechanisms remain uncharted. Employing murine and macrophage (RAW264.7) cellular models subjected to polystyrene nanoplastics (PS-NPs), our investigative approach encompassed an array of techniques: Cell Counting Kit-8 assays, flow cytometric analysis, acridine orange/ethidium bromide (AO/EB) fluorescence staining, cell transfection, cell cycle scrutiny, genetic manipulation, messenger RNA expression profiling via quantitative real-time PCR, and protein expression evaluation through western blotting. The results showed that PS-NPs caused RAW264.7 cell apoptosis, leading to cell cycle arrest, and activated the cGAS-STING pathway. This resulted in NF-κB signaling activation and increased pro-inflammatory mediator expression. Importantly, PS-NPs-induced activation of NF-κB and its downstream inflammatory cascade were markedly diminished after the silencing of the STING gene. Our findings highlight the critical role of the cGAS-STING pathway in the immunotoxic effects induced by PS-NPs. We outline a new mechanism whereby nanoplastics may trigger dysregulated innate immune and inflammatory responses via the cGAS/STING pathway.

RNA N6-Methyladenosine Modification in DNA Damage Response and Cancer Radiotherapy.

The N6-methyladenosine (M6A) modification is the most common internal chemical modification of RNA molecules in eukaryotes. This modification can affect mRNA metabolism, regulate RNA transcription, nuclear export, splicing, degradation, and translation, and significantly impact various aspects of physiology and pathobiology. Radiotherapy is the most common method of tumor treatment. Different intrinsic cellular mechanisms affect the response of cells to ionizing radiation (IR) and the effectiveness of cancer radiotherapy. In this review, we summarize and discuss recent advances in understanding the roles and mechanisms of RNA M6A methylation in cellular responses to radiation-induced DNA damage and in determining the outcomes of cancer radiotherapy. Insights into RNA M6A methylation in radiation biology may facilitate the improvement of therapeutic strategies for cancer radiotherapy and radioprotection of normal tissues.

TAB182 regulates glycolytic metabolism by controlling LDHA transcription to impact tumor radiosensitivity.

Metabolic reprogramming, a hallmark of cancer, is closely associated with tumor development and progression. Changes in glycolysis play a crucial role in conferring radiation resistance to tumor cells. How radiation changes the glycolysis status of cancer cells is still unclear. Here we revealed the role of TAB182 in regulating glycolysis and lactate production in cellular response to ionizing radiation. Irradiation can significantly stimulate the production of TAB182 protein, and inhibiting TAB182 increases cellular radiosensitivity. Proteomic analysis indicated that TAB182 influences several vital biological processes, including multiple metabolic pathways. Knockdown of TAB182 results in decreased lactate production and increased pyruvate and ATP levels in cancer cells. Moreover, knocking down TAB182 reverses radiation-induced metabolic changes, such as radioresistant-related lactate production. TAB182 is necessary for activating LDHA transcription by affecting transcription factors SP1 and c-MYC; its knockdown attenuates the upregulation of LDHA by radiation, subsequently suppressing lactate production. Targeted suppression of TAB182 significantly enhances the sensitivity of murine xenograft tumors to radiotherapy. These findings advance our understanding of glycolytic metabolism regulation in response to ionizing radiation, which may offer significant implications for developing new strategies to overcome tumor radioresistance.

Radiation-targeted immunotherapy: A new perspective in cancer radiotherapy.

In contemporary oncology, radiation therapy and immunotherapy stand as critical treatments, each with distinct mechanisms and outcomes. Radiation therapy, a key player in cancer management, targets cancer cells by damaging their DNA with ionizing radiation. Its effectiveness is heightened when used alongside other treatments like surgery and chemotherapy. Employing varied radiation types like X-rays, gamma rays, and proton beams, this approach aims to minimize damage to healthy tissue. However, it is not without risks, including potential damage to surrounding normal cells and side effects ranging from skin inflammation to serious long-term complications. Conversely, immunotherapy marks a revolutionary step in cancer treatment, leveraging the body's immune system to target and destroy cancer cells. It manipulates the immune system's specificity and memory, offering a versatile approach either alone or in combination with other treatments. Immunotherapy is known for its targeted action, long-lasting responses, and fewer side effects compared to traditional therapies. The interaction between radiation therapy and immunotherapy is intricate, with potential for both synergistic and antagonistic effects. Their combined use can be more effective than either treatment alone, but careful consideration of timing and sequence is essential. This review explores the impact of various radiation therapy regimens on immunotherapy, focusing on changes in the immune microenvironment, immune protein expression, and epigenetic factors, emphasizing the need for personalized treatment strategies and ongoing research to enhance the efficacy of these combined therapies in cancer care.

Predictive metabolomic signatures for safety assessment of three plastic nanoparticles using intestinal organoids.

Nanoplastic particles are pervasive environmental contaminants with potential health risks, while mouse intestinal organoids provide accurate in vitro models for studying these interactions. Metabolomics, especially through LC-MS, enables detailed cellular response studies, and there's a novel interest in comparing metabolic changes across nanoparticle species using gut organoids. This study used a mouse intestinal organoid combined with cell model to explore the differences in metabolites and toxicity mechanisms induced by exposure to three nanoplastics (PS, PTFE, and PMMA). The results showed that PS, PTFE, and PMMA exposure reduced mitochondrial membrane potential, intracellular ROS accumulation and oxidative stress, and inhibited the AKT/mTOR signaling pathway. Non-targeted metabolomics results confirmed that three types of nanoplastic particles regulate cellular status by regulating fatty acid metabolism, nucleotide metabolism, necroptosis and autophagy pathways. More importantly, these representative metabolites were further validated in model groups after mouse intestinal organoids and HCT116 cells were exposed to the respective NPs, indicating that organoid metabolomics results can be used to effectively predict toxicity. Untargeted metabolomics is sensitive enough to detect subtle metabolomic changes when functional cellular analysis shows no significant differences. Overall, our study reveals the underlying metabolic mechanism of NPs-induced intestinal organoid toxicity and provides new insights into the possible adverse consequences of NPs.

Lactate exacerbates lung damage induced by nanomicroplastic through the gut microbiota-HIF1a/PTBP1 pathway.

Exposure to nanomicroplastics (nano-MPs) can induce lung damage. The gut microbiota is a critical modulator of the gut-lung axis. However, the mechanisms underlying these interactions have not been elucidated. This study explored the role of lactate, a key metabolite of the microbiota, in the development of lung damage induced by nano-MPs (LDMP). After 28 days of exposure to nano-MPs (50-100 nm), mice mainly exhibited damage to the lungs and intestinal mucosa and dysbiosis of the gut microbiota. Lactate accumulation was observed in the lungs, intestines and serum and was strongly associated with the imbalance in lactic acid bacteria in the gut. Furthermore, no lactate accumulation was observed in germ-free mice, while the depletion of the gut microbiota using a cocktail of antibiotics produced similar results, suggesting that lactate accumulation in the lungs may have been due to changes in the gut microbiota components. Mechanistically, elevated lactate triggers activation of the HIF1a/PTBP1 pathway, exacerbating nano-MP-induced lung damage through modulation of the epithelial-mesenchymal transition (EMT). Conversely, mice with conditional knockout of Ptbp1 in the lungs (Ptbp1flfl) and PTBP1-knockout (PTBP1-KO) human bronchial epithelial (HBE) cells showed reversal of the effects of lactate through modulation of the HIF1a/PTBP1 signaling pathway. These findings indicate that lactate is a potential target for preventing and treating LDMP.

Downregulation of TAB182 promotes cancer stem-like cell properties and therapeutic resistance in triple-negative breast cancer cells.

TAB182 participates in DNA damage repair and radio-/chemosensitivity regulation in various tumors, but its role in tumorigenesis and therapeutic resistance in breast cancer remains unclear. In the current paper, we observed that triple-negative Breast Cancer (TNBC), a highly aggressive type of breast cancer, exhibits a lower expression of TAB182. TAB182 knockdown stimulates the proliferation, migration, and invasion of TNBC cells. Our study first obtained RNA-seq data to explore the cellular functions mediated by TAB182 at the genome level in TNBC cells. A transcriptome analysis and in vitro experiments enabled us to identify that TAB182 downregulation drives the enhanced properties of cancer stem-like cells (CSCs) in TNBC cells. Furthermore, TAB182 deletion contributes to the resistance of cells to olaparib or cisplatin, which can be rescued by silencing GLI2, a gene downstream of cancer stemness-related signaling pathways. Our results reveal a novel function of TAB182 as a potential negative regulator of cancer stem-like properties and drug sensitivity in TNBC cells, suggesting that TAB182 may be a tumor suppressor gene and is associated with increased therapeutic benefits for TNBC patients.

Double-strand DNA break repair: molecular mechanisms and therapeutic targets.

Double-strand break (DSB), a significant DNA damage brought on by ionizing radiation, acts as an initiating signal in tumor radiotherapy, causing cancer cells death. The two primary pathways for DNA DSB repair in mammalian cells are nonhomologous end joining (NHEJ) and homologous recombination (HR), which cooperate and compete with one another to achieve effective repair. The DSB repair mechanism depends on numerous regulatory variables. DSB recognition and the recruitment of DNA repair components, for instance, depend on the MRE11-RAD50-NBS1 (MRN) complex and the Ku70/80 heterodimer/DNA-PKcs (DNA-PK) complex, whose control is crucial in determining the DSB repair pathway choice and efficiency of HR and NHEJ. In-depth elucidation on the DSB repair pathway's molecular mechanisms has greatly facilitated for creation of repair proteins or pathways-specific inhibitors to advance precise cancer therapy and boost the effectiveness of cancer radiotherapy. The architectures, roles, molecular processes, and inhibitors of significant target proteins in the DSB repair pathways are reviewed in this article. The strategy and application in cancer therapy are also discussed based on the advancement of inhibitors targeted DSB damage response and repair proteins.

Diverse applications and development of aptamer detection technology.

Aptamers have received extensive attention in recent years because of their advantages of high specificity, high sensitivity and low immunogenicity. Aptamers can perform almost all functions of antibodies through the combination of spatial structure and target, which are called "chemical antibodies". At present, aptamers have been widely used in cell imaging, new drug development, disease treatment, microbial detection and other fields. Due to the diversity of modifications, aptamers can be combined with different detection technologies to construct aptasensors. This review focuses on the diversity of aptamers in the field of detection and the development of aptamer-based detection technology and proposes new challenges for aptamers in this field.

Deficiency of salt-inducible kinase 2 (SIK2) promotes immune injury by inhibiting the maturation of lymphocytes.

Salt-inducible kinase 2 (SIK2) belongs to the serine/threonine protein kinases of the AMPK/SNF1 family, which has important roles in cell cycle, tumor, melanogenesis, neuronal damage repair and apoptosis. Recent studies showed that SIK2 regulates the macrophage polarization to make a balance between inflammation and macrophage. Macrophage is critical to initiate immune regulation, however, whether SIK2 can be involved in immune regulation is not still well understood. Here, we revealed that the protein of SIK2 was highly expressed in thymus, spleen, lung, and brain. And SIK2 protein content increased in RAW264.7 and AHH1 cells with a time and dose-dependent after-ionizing radiation (IR). Inhibition of SIK2 could promote AHH1 cells apoptosis Moreover, we used the Cre-LoxP system to construct the SIK2+/- mice, and the research on function suggested that the deficiency of SIK2 could promote the sensitivity of IR. The deficiency of SIK2 promoted the immune injury via inhibiting the maturation of T cells and B cells. Furthermore, the TCRß rearrangement was inhibited by the deficiency of SIK2. Collectively, this study demonstrated that SIK2 provides an essential function of regulating immune injury, which will provide new ideas for the treatment of immune injury-related diseases.