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Histone methylation can affect chromosome structure and binding to other proteins, depending on the type of amino acid being modified and the number of methyl groups added, this modification may promote transcription of genes (H3K4me2, H3K4me3, and H3K79me3) or reduce transcription of genes (H3K9me2, H3K9me3, H3K27me2, H3K27me3, and H4K20me3). In addition, advances in tumor immunotherapy have shown that histone methylation as a type of protein post-translational modification is also involved in the proliferation, activation and metabolic reprogramming of immune cells in the tumor microenvironment. These post-translational modifications of proteins play a crucial role in regulating immune escape from tumors and immunotherapy. Lysine methyltransferases are important components of the post-translational histone methylation modification pathway. Lysine methyltransferase 2C (KMT2C), also known as MLL3, is a member of the lysine methyltransferase family, which mediates the methylation modification of histone 3 lysine 4 (H3K4), participates in the methylation of many histone proteins, and regulates a number of signaling pathways such as EMT, p53, Myc, DNA damage repair and other pathways. Studies of KMT2C have found that it is aberrantly expressed in many diseases, mainly tumors and hematological disorders. It can also inhibit the onset and progression of these diseases. Therefore, KMT2C may serve as a promising target for tumor immunotherapy for certain diseases. Here, we provide an overview of the structure of KMT2C, disease mechanisms, and diseases associated with KMT2C, and discuss related challenges.
Subject(s)
Neoplasms , Humans , Neoplasms/immunology , Neoplasms/therapy , Methylation , Protein Processing, Post-Translational , Animals , Histone-Lysine N-Methyltransferase/metabolism , Histone-Lysine N-Methyltransferase/genetics , Histones/metabolism , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Tumor Microenvironment/immunology , Neoplasm Proteins/genetics , Neoplasm Proteins/immunology , Neoplasm Proteins/metabolism , Gene Expression Regulation, NeoplasticABSTRACT
BACKGROUND: Joint replacement is a common treatment for older patients with high incidences of hip joint diseases. However, postoperative recovery is slow and complications are common, which reduces surgical effectiveness. Therefore, patients require long-term, high-quality, and effective nursing interventions to promote rehabilitation. Continuity of care has been used successfully in other diseases; however, little research has been conducted on older patients who have undergone hip replacement. AIM: To explore the clinical effect of continuous nursing on rehabilitation after discharge of older individuals who have undergone joint replacement. METHODS: A retrospective analysis was performed on the clinical data of 113 elderly patients. Patients receiving routine nursing were included in the convention group (n = 60), and those receiving continuous nursing, according to various methods, were included in the continuation group (n = 53). Harris score, short form 36 (SF-36) score, complication rate, and readmission rate were compared between the convention and continuation groups. RESULTS: After discharge, Harris and SF-36 scores of the continuation group were higher than those of the convention group. The Harris and SF-36 scores of the two groups showed an increasing trend with time, and there was an interaction effect between group and time (Harris score: F intergroup effect = 376.500, F time effect = 20.090, F interaction effect = 4.824; SF-36 score: F intergroup effect = 236.200, F time effect = 16.710, F interaction effect = 5.584; all P < 0.05). Furthermore, the total complication and readmission rates in the continuation group were lower (P < 0.05). CONCLUSION: Continuous nursing could significantly improve hip function and quality of life in older patients after joint replacement and reduce the incidence of complications and readmission rates.
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BACKGROUND: Irinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from Huangqin Decoction (HQD) have been proven to enhance the anticancer activity of CPT-11 in our previous study. OBJECTIVE: This study aimed to determine the optimal combination of the four components for sensitizing CPT-11 as well as to explore the underlying mechanism. METHODS: The orthogonal design method was applied to obtain candidate combinations (Cmb1-9) of the four components. The influence of different combinations on the anticancer effect of CPT-11 was first evaluated in vitro by cell viability, wound healing ability, cloning formation, apoptosis, and cell cycle arrest. Then, a CRC xenograft mice model was constructed to evaluate the anticancer effect of the optimal combination in vivo. Potential mechanisms of the optimal combination exerting a sensitization effect combined with CPT-11 against CRC were analyzed by targeted metabolomics. RESULTS: In vitro experiments determined that Cmb8 comprised of baicalin, baicalein, wogonin, and glycyrrhizic acid at the concentrations of 17 µM, 47 µM, 46.5 µM and 9.8 µM respectively was the most effective combination. Importantly, the cell viability assay showed that Cmb8 exhibited synergistic anticancer activity in combination with CPT-11. In in vivo experiments, this combination (15 mg/kg of baicalin, 24 mg/kg of baicalein, 24 mg/kg of wogonin, and 15 mg/kg of glycyrrhizic acid) also showed a synergistic anticancer effect. Meanwhile, inflammatory factors and pathological examination of the colon showed that Cmb8 could alleviate the gastrointestinal damage induced by CPT-11. Metabolic profiling of the tumors suggested that the synergistic anticancer effect of Cmb8 might be related to the regulation of fatty acid metabolism. CONCLUSION: The optimal combination of four components derived from HQD for the synergistic sensitization of CPT-11 against CRC was identified.
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Aqueous nickel-ion batteries (ANIBs) as an emerging energy storage device attracted much attention owing to their multielectron redox reaction and dendrite-free Ni anode, yet their development is hindered by the divalent properties of Ni2+ and the lack of suitable cathode materials. Herein, a hydrated iron vanadate (Fe2V3O10.5â1.5H2O, FOH) with a preferred orientation along the (200) plane is innovatively proposed and used as cathode material for ANIBs. The FOH cathode exhibits a remarkable capacity of 129.3 mAh g-1 at 50 mA g-1 and a super-high capacity retention of 95% at 500 mA g-1 after 700 cycles. The desirable Ni2+ storage capacity of FOH can be attributed to the preferentially oriented and tunnel structures, which offer abundant reaction active planes and a broad Ni2+ diffusion path, the abundant vacancies and high specific surface area further increase ion storage sites and accelerate ion diffusion in the FOH lattice. Furthermore, the Ni2+ storage mechanism and structural evolution in the FOH cathode are explored through ex situ XRD, ex situ Raman, ex situ XPS and other ex situ characteristics. This work opens a new way for designing novel cathode materials to promote the development of ANIBs.
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A visible light-mediated azidation of α-diazoesters with TMSN3 to synthesize valuable α-azidoesters has been developed. Without using any catalysts and additives, the reaction proceeded smoothly under visible light irradiation at room temperature. A variety of α-diazoesters were successfully converted to the desired α-azidoesters, showing good functional group tolerance. The products could be readily transformed into triazole, α-azidoacid, and α-azidoamide. Mechanistic studies suggested that the reaction is mainly carrying out via direct photoexcitation and SH2 mechanism. This work provides a novel, mild, and practical protocol for synthesizing α-azidoesters.
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Objective: To evaluate the impact of Pender-based health education on outcomes in rivaroxaban-treated lower limb DVT patients. Methods: 103 patients with DVT of the lower limbs treated with rivaroxaban admitted to The First Affiliated Hospital of Xi'an Jiaotong University from January 2022 to January 2023 were included in the study and were randomly divided into the conventional group (n=52, receiving routine care with medication instruction, exercise instruction, and psychological care as the main components) and the Pender group (n=51, giving health education based on the Pender health promotion model in addition to conventional care) to compare the recurrence rate of DVT of the lower limbs, DVT of the lower limbs clinical condition, complication rate, quality of life score, coagulation index and nursing satisfaction rate in the two groups. Primary results: The recurrence rate of lower limb DVT, circumference of the affected limb, time to get out of bed, and time to reduce swelling in the Pender group were lower (shorter) than those in the conventional group (P < .05); after the intervention, all quality of life scores in the Pender group were higher than those in the conventional group (P < .05). Secondary results: The complication rate, fibrinogen (FIB) and D-dimer (D-D) levels were lower (shorter) in the Pender group than in the conventional group (P < .05). After the intervention, the levels of activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) were higher in the Pender group than in the conventional group (P < .05). Conclusion: The health education based on the Pender health promotion model is effective in patients with lower limb DVT treated with rivaroxaban, which can effectively reduce recurrence and complications, optimize coagulation indexes, and improve the quality of life and nursing care satisfaction by improving the patients' health cognition and health behaviors, which is of great value in clinical application and promotion.
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BACKGROUND: Increased level of serum cholic acid (CA) is often accompanied with decreased CYP2E1 expression in hepatocellular carcinoma (HCC) patients. However, the roles of CA and CYP2E1 in hepatocarcinogenesis have not been elucidated. This study aimed to investigate the roles and the underlying mechanisms of CYP2E1 and CA in HCC cell growth. METHODS: The proteomic analysis of liver tumors from DEN-induced male SD rats with CA administration was used to reveal the changes of protein expression in the CA treated group. The growth of CA-treated HCC cells was examined by colony formation assays. Autophagic flux was assessed with immunofluorescence and confocal microscopy. Western blot analysis was used to examine the expression of CYP2E1, mTOR, AKT, p62, and LC3II/I. A xenograft tumor model in nude mice was used to examine the role of CYP2E1 in CA-induced hepatocellular carcinogenesis. The samples from HCC patients were used to evaluate the clinical value of CYP2E1 expression. RESULTS: CA treatment significantly increased the growth of HCC cells and promoted xenograft tumors accompanied by a decrease of CYP2E1 expression. Further studies revealed that both in vitro and in vivo, upregulated CYP2E1 expression inhibited the growth of HCC cells, blocked autophagic flux, decreased AKT phosphorylation, and increased mTOR phosphorylation. CYP2E1 was involved in CA-activated autophagy through the AKT/mTOR signaling. Finally, decreased CYP2E1 expression was observed in the tumor tissues of HCC patients and its expression level in tumors was negatively correlated with the serum level of total bile acids (TBA) and gamma-glutamyltransferase (GGT). CONCLUSIONS: CYP2E1 downregulation contributes to CA-induced HCC development presumably through autophagy regulation. Thus, CYP2E1 may serve as a potential target for HCC drug development.
Subject(s)
Autophagy , Carcinoma, Hepatocellular , Cell Proliferation , Cholic Acid , Cytochrome P-450 CYP2E1 , Liver Neoplasms , Animals , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/chemically induced , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Liver Neoplasms/chemically induced , Humans , Cytochrome P-450 CYP2E1/metabolism , Cytochrome P-450 CYP2E1/genetics , Male , Autophagy/drug effects , Cell Line, Tumor , Rats , Cell Proliferation/drug effects , Mice , Rats, Sprague-Dawley , Signal Transduction , Proteomics/methods , Disease Models, Animal , Mice, NudeABSTRACT
Objectives: To determine risk factors for the occurrence of adverse outcomes in patients with new-onset refractory status epilepsy (NORSE) and to construct a concomitant nomogram. Methods: Seventy-six adult patients with NORSE who were admitted to the Department of Neurology, First Affiliated Hospital of Sun Yat-sen University between January 2016 and December 2022 were enrolled for the study. Participants were divided into two-those with good and poor functional outcomes-and their pertinent data was obtained from the hospital medical recording system. Univariate analysis was used to identify potential causes of poor outcomes in both groups and a multivariate logistic regression model was used to identify risk factors for the occurrence of poor outcomes. Using the R programming language RMS package, a nomogram was created to predict the occurrence of poor outcomes. Results: The NORSE risk of adverse outcome nomogram model included four predictors, namely duration of mechanical ventilation (OR = 4.370, 95% CI 1.221-15.640, p = 0.023), antiviral therapy (OR = 0.045, 95% CI 0.005-0.399, p = 0.005), number of anesthetics (OR = 13.428, 95% CI 2.16-83.48, p = 0.005) and neutrophil count/lymphocyte count ratio (NLR) (OR = 5.248, 95% CI 1.509-18.252, p = 0.009). The nomogram had good consistency and discrimination in predicting risk and can thus assist clinical care providers to assess outcomes for NORSE patients. Through ordinary bootstrap analyses, the results of the original set prediction were confirmed as consistent with those of the test set. Conclusion: The nomogram model of risk of adverse outcomes in NORSE adult patients developed in this study can facilitate clinicians to predict the risk of adverse outcomes in NORSE patients and make timely and reasonable interventions for patients at high risk of adverse outcomes.
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The effect of interface dislocation networks on the mechanical properties of new Ni-based single crystal alloys containing Rhenium (Re) is very large. Because the interface dislocations are microscopic in the nano-scale range, this has not been investigated, and it is very difficult to prepare new Ni-based single crystal alloys containing Re. Therefore, six kinds of new Ni-based single crystal alloys containing Re were prepared, and the hardness tests and nonlinear ultrasonic lamb wave tests were performed on the samples. It was found that the density of interface dislocation networks increases with the increase in the content of Re, which improves the blocking ability of matrix phase dislocation cutting into precipitated phase and enhances the inhibition of dislocation movement. The nonlinear ultrasonic lamb wave tests showed that the materials exhibit better mechanical properties when the density of the interface dislocation networks increases. Meanwhile, a new molecular dynamics model which is closer to the real state of an Ni-based single crystal alloy was constructed to reveal the evolution mechanism of interface dislocation networks. The results showed that the potential energy of Re atoms at the interface is the lowest, which affects the reduction of the potential energy of other atoms at the interface, and thus the stability of the model is improved. In addition, according to the change in the total length of dislocation loops in the model system, with the increase in the content of Re atoms, the inhibition of dislocation movement by dislocation networks at the interface is strengthened.
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Herein, a straightforward protocol was developed for the one-pot synthesis of N-doped lignosulfonate-derived carbons (NLDCs) with a tunable porous structure using natural amino acids-templated self-assembly strategy. Specifically, histidine was employed as a template reagent, leading to the preparation of 10-NLDC-21 with remarkable characteristics, including the large specific surface area (SBET = 1844.5 m2/g), pore volume (Vmes = 1.22 cm3/g) and efficient adsorption for atrazine (ATZ) removal. The adsorption behavior of ATZ by NLDCs followed the Langmuir and pseudo-second-order models, suggesting a monolayer chemisorption nature of ATZ adsorption with the maximum adsorption capacity reached up to 265.77 mg/g. Furthermore, NLDCs exhibited excellent environmental adaptability and recycling performance. The robust affinity could be attributed to multi-interactions including pore filling, electrostatic attraction, hydrogen bonding and π-π stacking between the adsorbents and ATZ molecules. This approach offers a practical method for exploring innovative bio-carbon materials for sewage treatment.
Subject(s)
Atrazine , Carbon , Lignin , Water Pollutants, Chemical , Atrazine/chemistry , Lignin/chemistry , Lignin/analogs & derivatives , Porosity , Adsorption , Carbon/chemistry , Hydrogen-Ion Concentration , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/isolation & purification , Water Purification/methods , KineticsABSTRACT
AIMS: This study was designed to investigate the role of growth arrest and DNA damage-inducible ß (GADD45B) in modulating fear memory acquisition and elucidate its underlying mechanisms. MAIN METHODS: Adeno-associated virus (AAV) that knockdown or overexpression GADD45B were injected into ventral hippocampal CA1 (vCA1) by stereotactic, and verified by fluorescence and Western blot. The contextual fear conditioning paradigm was employed to examine the involvement of GADD45B in modulating aversive memory acquisition. The Y-maze and novel location recognition (NLR) tests were used to examine non-aversive cognition. The synaptic plasticity and electrophysiological properties of neurons were measured by slice patch clamp. KEY FINDINGS: Knockdown of GADD45B in the vCA1 significantly enhanced fear memory acquisition, accompanied by an upregulation of long-term potentiation (LTP) expression and intrinsic excitability of vCA1 pyramidal neurons (PNs). Conversely, overexpression of GADD45B produced the opposite effects. Notably, silencing the activity of vCA1 neurons abolished the impact of GADD45B knockdown on fear memory development. Moreover, mice with vCA1 GADD45B overexpression exhibited impaired spatial cognition, whereas mice with GADD45B knockdown did not display such impairment. SIGNIFICANCE: These results provided compelling evidence for the crucial involvement of GADD45B in the formation of aversive memory and spatial cognition.
Subject(s)
CA1 Region, Hippocampal , Fear , GADD45 Proteins , Mice, Inbred C57BL , Animals , Male , Fear/physiology , Mice , CA1 Region, Hippocampal/metabolism , CA1 Region, Hippocampal/physiology , Cognition/physiology , Memory/physiology , Long-Term Potentiation/physiology , Maze Learning/physiology , Neuronal Plasticity/physiology , Antigens, Differentiation/metabolism , Antigens, Differentiation/genetics , Gene Knockdown TechniquesABSTRACT
Hyperuricemia (HUA), a severe metabolic disease derived from purine metabolism disorder, will lead to abnormally increased serum uric acid (SUA) levels in the body. Studies have shown that HUA is highly related to gout, hypertension, diabetes, coronary heart disease, chronic kidney diseases, and so on. Traditional Chinese medicine (TCM) shows excellent results in treating HUA because of its unique advantages of multi-metabolites and multi-targets. This article reports on the use of TCM components for uric acid (UA)-lowering activity with excellent efficacy and low side effects based on established HUA models. This work summarizes the advantages and limitations of various HUA disease models for efficacy evaluation. Applications of TCM in HUA treatment have also been discussed in detail. This paper reveals recent research progress on HUA in constructing evaluation models and systematic TCM interventions. It will provide a scientific reference for establishing the HUA model and suggest future TCM-related HUA studies.
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A photocatalytic cross-dehydrogenative coupling of diarylphosphine oxides with alcohols and phenols has been developed. Using organic dye Rose Bengal as the photocatalyst and air as the oxidant, the reaction proceeded smoothly at room temperature. Both alcohols and phenols were feasible, affording various organophosphinates in high yields. The absence of a halogenating reagent, the absence of a transition-metal catalyst, a green oxidant, and mild conditions make this strategy environmentally benign and sustainable. Mechanistic studies indicated that the reaction is enabled by the cooperation of photoredox catalysis and photosensitization.
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OBJECTIVES: This comprehensive review aimed to compile cases of patients with thymoma diagnosed with both autoimmune encephalitis (AE) and myasthenia gravis (MG), and describe their clinical characteristics. METHODS: Clinical records of 3 AE patients in the first affiliated hospital of Sun Yat-sen University were reviewed. All of them were diagnosed with AE between 1 November 2021 and 1 March 2022, and clinical evidence about thymoma and MG was found. All published case reports were searched for comprehensive literature from January 1990 to June 2022. RESULTS: A total of 18 cases diagnosed with thymoma-associated autoimmune encephalitis (TAAE) and thymoma-associated myasthenia gravis (TAMG) were included in this complication, wherein 3 cases were in the first affiliated hospital of Sun Yat-sen University and the other 15 were published case reports. 5/18 patients had alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antibody (AMPAR-Ab) in their serum and cerebrospinal fluid (CSF). All of them had positive anti-acetylcholine receptor antibody (AChR-Ab). And 12/18 patients showed a positive response to thymectomy and immunotherapy. Besides, thymoma recurrences were detected because of AE onset. And the shortest interval between operation and AE onset was 2 years in patients with thymoma recurrence. CONCLUSIONS: There was no significant difference in the clinical manifestations between these patients and others with only TAMG or TAAE. TAAE was commonly associated with AMPAR2-Ab. Significantly, AE more commonly heralded thymoma recurrences than MG onset. And the intervals of thymectomy and MG or AE onset had different meanings for thymoma recurrence and prognoses of patients.
Subject(s)
Encephalitis , Hashimoto Disease , Myasthenia Gravis , Thymoma , Thymus Neoplasms , Humans , Thymoma/complications , Thymoma/diagnosis , Thymoma/surgery , Thymus Neoplasms/complications , Thymus Neoplasms/diagnosis , Thymus Neoplasms/surgery , Myasthenia Gravis/complications , Myasthenia Gravis/therapy , Encephalitis/therapy , Encephalitis/complicationsABSTRACT
The growth arrest and DNA damage inducible protein 45 (GADD45) family comprises stress-induced nuclear proteins that interact with DNA demethylases to facilitate DNA demethylation, thereby regulating diverse cellular processes including oxidative stress, DNA damage repair, apoptosis, proliferation, differentiation, inflammation, and neuroplasticity by modulating the expression patterns of specific genes. Widely expressed in the central nervous system, the GADD45 family plays a pivotal role in various neurological disorders, rendering it a potential therapeutic target for central nervous system diseases. This review presented a comprehensive overview of the expression patterns and potential mechanisms of action associated with each member of GADD45 family (GADD45α, GADD45ß, and GADD45γ) in neurodevelopmental, neurodegenerative, and neuropsychiatric disorders, while also explored strategies to harness these mechanisms for intervention and treatment. Future research should prioritize the development of effective modulators targeting the GADD45 family for clinical trials aimed at treating central nervous system diseases.
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Dry eye is a widespread chronic inflammatory disease that causes fatigue, tingling, burning, and other symptoms. Dry eye is attributed to rheumatic diseases, diabetes, hormone disorders, and contact lenses, which activate inflammatory pathways: mitogen-activated protein kinases (MAPK) and nuclear factor-B (NF-κB), promote macrophage inflammatory cell and T cell activation, and inflammation factors. Clinicians use a combination of anti-inflammatory drugs to manage different symptoms of dry eye; some of these anti-inflammatory drugs are being developed. This review introduces the dry eye inflammation mechanisms and the involved inflammatory factors. We also elucidate the anti-inflammatory drug mechanism and the detection limits.
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Age-related macular degeneration is a retinal disease that causes permanent loss of central vision in people over the age of 65. Its pathogenesis may be related to mitochondrial dysfunction, inflammation, apoptosis, autophagy, complement, intestinal flora, and lipid disorders. In addition, the patient's genes, age, gender, cardiovascular disease, unhealthy diet, and living habits may also be risk factors for this disease. Complement proteins are widely distributed in serum and tissue fluid. In the early 21st century, a connection was found between the complement cascade and age-related macular degeneration. However, little is known about the effect of complement factors on the pathogenesis of age-related macular degeneration. This article reviews the factors associated with age-related macular degeneration, the relationship between each factor and complement, the related functions, and variants and provides new ideas for the treatment of this disease.
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Excessive use of antithyroid drug methimazole (MMI) in pharmaceutical samples can cause hypothyroidism and symptoms of metabolic decline. Hence, it is urgent to develop rapid, low cost and accurate colorimetric method with peroxidase-like nanozymes for determination of MMI in medical, nutrition and pharmaceutical studies. Herein, Fe single atoms were facilely encapsulated into N, P-codoped carbon nanosheets (Fe SAs/NP-CSs) by a simple pyrolysis strategy, as certified by a series of characterizations. UV-vis absorption spectroscopy was employed to illustrate the high peroxidase-mimicking activity of the resultant Fe SAs/NP-CSs nanozyme through the typical catalysis of 3,3',5,5'-tetramethylbenzidine (TMB) oxidation. The catalytic mechanism was scrutionously investigated by the fluorescence spectroscopy and electron paramagnetic resonance (EPR) tests. Additionally, the introduced MMI had the ability to reduce the oxidation of TMB (termed oxTMB) as a peroxidase inhibitor, coupled by fading the blue color. By virtue of the above findings, a visual colorimetric sensor was established for dual detection of methimazole (MMI) with a linear scope of 5-50 mM and a LOD of 1.57 mM, coupled by assay of H2O2 at a linear range of 3-50 mM. According to the irreversible oxidation of the drug, its screening with acceptable results was achieved on the sensing platform even in commercial tablets The Fe SAs/NP-CSs nanozyme holds great potential for clinical diagnosis and drug analysis.
Subject(s)
Carbon , Colorimetry , Carbon/chemistry , Colorimetry/methods , Methimazole , Hydrogen Peroxide/analysis , Peroxidase/metabolism , Oxidoreductases , Peroxidases , Coloring Agents , Pharmaceutical PreparationsABSTRACT
The convenient and precise preparation of N,N'-diarylhydrazides, especially from readily available raw materials, remains highly challenging. Here, a photoredox catalytic phosphine-mediated deoxygenative hydroacylation of azobenzenes with abundant and readily available carboxylic acids has been developed. With Ir[dF(CF3)ppy]2(dtbbpy)PF6 as the photocatalyst, the reactions proceeded smoothly in the presence of PPh3 under visible light irradiation, delivering various N,N'-diarylhydrazides in up to 92% yields. Mechanistic studies revealed that the reaction proceeds via photoredox catalysis and phosphoranyl-radical-mediated C-O bond cleavage of carboxylic acids.
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Liver cancer, a common and intractable liver-related disease, is a malignant tumor with a high morbidity, which needs a high treatment cost but still lacks perfect clinical treatment methods. Looking for an effective platform for liver cancer study and drug screening is urgent and important. Traditional analytical methods for liver disease studies mainly rely on the 2D cell culture and animal experiments, which both cannot fully recapitulate physiological and pathological processes of human liver. For example, cell culture can only show basic functions of cells in vitro, while animal models always hold the problem of species divergence. The organoids, a 3D invitro culture system emerged in recent years, is a cell-bound body with different cell types and has partial tissue functions. The organoid technology can reveal the growth state, structure, function and characteristics of the tissue or organ, and plays an important role in reconstructing invitro experimental models that can truly simulate the human liver. In this paper, we will give a brief introduction of liver organoids and review their applications in liver cancer research, especially in liver cancer pathogenesis, drug screening, precision medicine, regenerative medicine, and other fields. We have also discussed advantages and disadvantages of organoids, as well as future directions and perspectives towards liver organoids.