AGO2 Protects Against Diabetic Cardiomyopathy by Activating Mitochondrial Gene Translation.

BACKGROUND: Diabetes is associated with cardiovascular complications. microRNAs translocate into subcellular organelles to modify genes involved in diabetic cardiomyopathy. However, functional properties of subcellular AGO2 (Argonaute2), a core member of miRNA machinery, remain elusive. METHODS: We elucidated the function and mechanism of subcellular localized AGO2 on mouse models for diabetes and diabetic cardiomyopathy. Recombinant adeno-associated virus type 9 was used to deliver AGO2 to mice through the tail vein. Cardiac structure and functions were assessed by echocardiography and catheter manometer system. RESULTS: AGO2 was decreased in mitochondria of diabetic cardiomyocytes. Overexpression of mitochondrial AGO2 attenuated diabetes-induced cardiac dysfunction. AGO2 recruited TUFM, a mitochondria translation elongation factor, to activate translation of electron transport chain subunits and decrease reactive oxygen species. Malonylation, a posttranslational modification of AGO2, reduced the importing of AGO2 into mitochondria in diabetic cardiomyopathy. AGO2 malonylation was regulated by a cytoplasmic-localized short isoform of SIRT3 through a previously unknown demalonylase function. CONCLUSIONS: Our findings reveal that the SIRT3-AGO2-CYTB axis links glucotoxicity to cardiac electron transport chain imbalance, providing new mechanistic insights and the basis to develop mitochondria targeting therapies for diabetic cardiomyopathy.

Nuclear AGO2 promotes myocardial remodeling by activating ANKRD1 transcription in failing hearts.

Heart failure (HF) is manifested by transcriptional and posttranscriptional reprogramming of critical genes. Multiple studies have revealed that microRNAs could translocate into subcellular organelles such as the nucleus to modify gene expression. However, the functional property of subcellular Argonaute2 (AGO2), the core member of the microRNA machinery, has remained elusive in HF. AGO2 was found to be localized in both the cytoplasm and nucleus of cardiomyocytes, and robustly increased in the failing hearts of patients and animal models. We demonstrated that nuclear AGO2 rather than cytosolic AGO2 overexpression by recombinant adeno-associated virus (serotype 9) with cardiomyocyte-specific troponin T promoter exacerbated the cardiac dysfunction in transverse aortic constriction (TAC)-operated mice. Mechanistically, nuclear AGO2 activates the transcription of ANKRD1, encoding ankyrin repeat domain-containing protein 1 (ANKRD1), which also has a dual function in the cytoplasm as part of the I-band of the sarcomere and in the nucleus as a transcriptional cofactor. Overexpression of nuclear ANKRD1 recaptured some key features of cardiac remodeling by inducing pathological MYH7 activation, whereas cytosolic ANKRD1 seemed cardioprotective. For clinical practice, we found ivermectin, an antiparasite drug, and ANPep, an ANKRD1 nuclear location signal mimetic peptide, were able to prevent ANKRD1 nuclear import, resulting in the improvement of cardiac performance in TAC-induced HF.

Mitochondrial damage-associated molecular patterns: A new insight into metabolic inflammation in type 2 diabetes mellitus.

The pathogenesis of diabetes is accompanied by increased levels of inflammatory factors, also known as "metabolic inflammation", which runs through the whole process of the occurrence and development of the disease. Mitochondria, as the key site of glucose and lipid metabolism, is often accompanied by mitochondrial function damage in type 2 diabetes mellitus (T2DM). Damaged mitochondria release pro-inflammatory factors through damage-related molecular patterns that activate inflammation pathways and reactions to oxidative stress, further aggravate metabolic disorders, and form a vicious circle. Currently, the pathogenesis of diabetes is still unclear, and clinical treatment focuses primarily on symptomatic intervention of the internal environment of disorders of glucose and lipid metabolism with limited clinical efficacy. The proinflammatory effect of mitochondrial damage-associated molecular pattern (mtDAMP) in T2DM provides a new research direction for exploring the pathogenesis and intervention targets of T2DM. Therefore, this review covers the most recent findings on the molecular mechanism and related signalling cascades of inflammation caused by mtDAMP in T2DM and discusses its pathogenic role of it in the pathological process of T2DM to search potential intervention targets.

Tunable Emission of Low-Dimensional Organic Metal Halides by Stoichiometric Ratio and Metal Center.

Low-dimensional (LD) organic metal halides (OMHs) have a bright future due to their excellent photoelectric characteristics and unique structure. However, the synthesis and emission control of LD-OMHs are still unclear. Herein, the different dimensional (zero-dimensional (0D), one-dimensional (1D), and three-dimensional (3D)) of OMHs were obtained by the reaction of 1,4-diazabicyclo (2.2.2) octane with PbBr2 in different stoichiometric ratios. This discovery shows that the structure and properties of OMHs can be regulated while maintaining the functional organic cations of OMHs, which broadens the path for the development of functional LD-OMHs. Among them, 0D-OMH 1 and 1D-OMH 3 have narrow-band (full width at half-maximum (fwhm) = 74 nm) and broad-band (fwhm = 201 nm) emission, respectively. We found that when organic cations have no contribution to the formation of conduction band minimum and valence band maximum, and the distances between polyhedrons are larger than the van der Waals diameter of the halogen atom, the effect of phonons on exciton transitions can be reduced to achieve a narrow-band emission. Further, Cu(I)- and Mn (II)-based 0D-OMHs were synthesized, which have high photoluminescence quantum yield (PLQY) (33.97 and 47.33%, respectively). When the emitting of 0D-OMHs produced by the interaction of the metal-center and halogens, the asymmetric planar metal-halogen structure will result in a higher PLQY.

Biomarker-driven targeted therapy in patients with recurrent platinum-resistant epithelial ovarian cancer (BRIGHT): protocol for an open-label, multicenter, umbrella study.

BACKGROUND: Platinum-resistant, recurrent ovarian cancer has an abysmal prognosis with limited treatment options. Poly-(ADP-ribose)-polymerase (PARP), angiogenesis, and immune checkpoint inhibitors might improve the outcomes of platinum-resistant, recurrent ovarian cancer, but accurate patient selections for those therapies remain a significant clinical challenge. PRIMARY OBJECTIVE: To evaluate the efficacy and safety of biomarker-driven combinatorial therapies of pamiparib, tislelizumab, bevacizumab, and nab-paclitaxel in platinum-resistant, recurrent ovarian cancer. STUDY HYPOTHESIS: A precision medicine combination of PARP inhibitors, anti-angiogenic therapy, immunotherapy, and chemotherapy will improve disease outcomes of platinum-resistant, recurrent ovarian cancer by accounting for genomic and immunologic features. TRIAL DESIGN: The BRIGHT Trial is a prospective, open-label, multicenter, phase II, umbrella study planning to enroll 160 patients with serous, endometrioid, or clear cell platinum-resistant, recurrent ovarian cancer from 11 clinical centers in China. Patients are assigned to one of three experimental arms based on biomarkers. Patients with BRCA1/2 mutations will receive pamiparib plus bevacizumab (arm 1, n=40) regardless of CD8+ tumor-infiltrating lymphocytes count. Patients with wild-type BRCA1/2 (BRCAwt) and ≥3 CD8+ tumor-infiltrating lymphocytes count will receive the combination of tislelizumab, bevacizumab, and nab-paclitaxel (arm 2, n=50), while BRCAwt patients with <3 CD8+ tumor-infiltrating lymphocytes count will receive bevacizumab plus dose-dense nab-paclitaxel (arm 3, n=50). After completing patient enrollment in arm 2, another 20 BRCAwt patients with ≥3 CD8+ tumor-infiltrating lymphocytes count will be included as an arm 2 expansion. Treatment will continue until disease progression or intolerable toxicity, and all adverse events will be recorded. MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients include those aged ≥18 with serous, endometrioid, or clear cell ovarian cancer, platinum-resistant recurrence, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. PRIMARY ENDPOINT: Objective response rate (ORR) assessed by the investigators by the RECIST 1.1 criteria. SAMPLE SIZE: 160 patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Recruitment is estimated to be completed by 2024 and results may be published by 2027. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05044871.

New Indole Alkaloids from the Fungus Talaromyces assiutensis JTY2.

Three new indole alkaloids, named talatensindoids A-C (1-3), together with two known biogenetically related indole alkaloids tryptamine (4) and L-tryptophan (5) were isolated from the Talaromyces assiutensis JTY2 based on the guidance of OSMAC approach. The structures of these indole alkaloids were determined by comprehensive spectroscopic analyses. The absolute configuration of 3 was confirmed by X-ray crystallographic analysis. Compound 1 represent the rare example of a chlorine-substituted indole alkaloid from natural products. The inhibitory activity of compounds 1-5 against two phytopathogenic fungi and three phytopathogenic bacteria was evaluated. Compound 1 exhibited broad spectrum antibacterial activities.

Expression analysis and targets prediction of microRNAs in OGD/R treated astrocyte-derived exosomes by smallRNA sequencing.

Astrocytes activate and crosstalk with neurons influencing inflammatory responses following ischemic stroke. The distribution, abundance, and activity of microRNAs in astrocytes-derived exosomes after ischemic stroke remains largely unknown. In this study, exosomes were extracted from primary cultured mouse astrocytes via ultracentrifugation, and exposed to oxygen glucose deprivation/re­oxygenation injury to mimic experimental ischemic stroke. SmallRNAs from astrocyte-derived exosomes were sequenced, and differentially expressed microRNAs were randomly selected and verified by stem-loop real time quantitative polymerase chain reaction. We found that 176 microRNAs, including 148 known and 28 novel microRNAs, were differentially expressed in astrocyte-derived exosomes following oxygen glucose deprivation/re­oxygenation injury. In gene ontology enrichment, Kyoto encyclopedia of genes and genomes pathway analyses, and microRNA target gene prediction analyses, these alteration in microRNAs were associated to a broad spectrum of physiological functions including signaling transduction, neuroprotection and stress responses. Our findings warrant further investigating of these differentially expressed microRNAs in human diseases particularly ischemic stroke.

Spartina alterniflora invasion altered phosphorus retention and microbial phosphate solubilization of the Minjiang estuary wetland in southeastern China.

Spartina alterniflora invasion is considered a critical event affecting sediment phosphorus (P) availability and stock. However, P retention and microbial phosphate solubilization in the sediments invaded with or without S. alterniflora have not been fully investigated. In this study, a sequential fractionation method and high-throughput sequencing were used to analyze P transformation and the underlying microbial mechanisms in the sediments of no plant (NP) zone, transition (T) zone, and plant (P) zone. Results showed that except for organic phosphate (OP), total phosphate (TP), inorganic phosphate (IP), and available phosphate (AP) all followed a significant decrease trend from the NP site to the T site, and to the P site. The vertical decrease of TP, IP, and AP was also observed with an increase in soil depth. Among the six IP fractions, Fe-P, Oc-P, and Ca10-P were the predominant forms, while the presence of S. alterniflora resulted in an obvious P depletion except for Ca8-P and Al-P. Although S. alterniflora invasion did not significantly alter the alpha diversity of phosphate-solubilizing bacteria (PSB) harboring phoD gene, several PSB belonging to p_Proteobacteria, p_Planctomycetes, and p_Cyanobacteriota showed close correlations with P speciation and IP fractions. Further correlation analysis revealed that the reduced soil pH, soil TN and soil EC, and the increased soil TOC mediated by the invasion of S. alterniflora also significantly correlated to these PSB. Overall, this study elucidates the linkage between PSB and P speciation and provides new insights into understanding P retention and microbial P transformation in the coastal sediment invaded by S. alterniflora.

Synthesis and Interlayer Assembly of a Graphenic Bowl with Peripheral Selenium Annulation.

Pentagonal cyclization at the bay positions of armchair-edged graphenic cores can build molecular bowls without the destruction of hexagonal lattices. However, this synthesis remains challenging due to unfavorable strain and the multiple reactions required. Here, we show that a new type of graphenic molecular bowl with a depth of 1.7 Å and a diameter of 1.2 nm is constructed by sextuple Se annulation at the bay positions of armchair-edged hexa-peri-hexabenzocoronene. This graphenic bowl is functionalized with phenylseleno groups that stack into a discrete bilayer dimer in solution. Such a dimer exhibits high stability and survives in the gas phase after laser ablation. Strikingly, the asymmetric one-dimensional supramolecular columns of graphenic bowl with coherent stacking configuration are observed in the solid state, which results in a strong second harmonic generation with prominent polarization dependence. Our findings present a concise synthesis of a giant molecular bowl with a graphenic core and demonstrate the unique supramolecular assembly of extended graphenic bowls.

Transcriptionally regulated miR-26a-5p may act as BRCAness in Triple-Negative Breast Cancer.

BACKGROUND: DNA damage and DNA damage repair (DDR) are important therapeutic targets for triple-negative breast cancer (TNBC), a subtype with limited chemotherapy efficiency and poor outcome. However, the role of microRNAs in the therapy is emerging. In this study, we explored whether miR-26a-5p could act as BRCAness and enhance chemotherapy sensitivity in TNBC. METHODS: Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-26a-5p in breast cancer tissues and cell lines. CCK-8 was used to measure drug sensitivity in concentration gradient and time gradient. Comet assay was used to detect DNA damage. Flow cytometry was performed to examine apoptosis. Moreover, we used western blot and immunofluorescence to detect biomarkers. Luciferase reporter assay was performed to verify the combination of miR-26a-5p and 3'UTR of target gene. Hormone deprivation and stimulation assay were used to validate the effect of hormone receptors on the expression of miR-26a-5p. Chromatin immunoprecipitation (ChIP) assays were used to verify the binding sites of ER-a or PR with the promoter of miR-26a-5p. Animal experiments were performed to the effect of miR-26a-5p on Cisplatin treatment. RESULTS: The expression of miR-26a-5p was significantly downregulated in TNBC. Overexpressing miR-26a-5p enhanced the Cisplatin-induced DNA damage and following apoptosis. Interestingly, miR-26a-5p promoted the expression of Fas without Cisplatin stimulating. It suggested that miR-26a-5p provided a hypersensitivity state of death receptor apoptosis and promoted the Cisplatin sensitivity of TNBC cells in vitro and in vivo. Besides, miR-26a-5p negatively regulated the expression of BARD1 and NABP1 and resulted in homologous recombination repair defect (HRD). Notably, overexpressing miR-26a-5p not only facilitated the Olaparib sensitivity of TNBC cells but also the combination of Cisplatin and Olaparib. Furthermore, hormone receptors functioned as transcription factors in the expression of miR-26a-5p, which explained the reasons that miR-26a-5p expressed lowest in TNBC. CONCLUSIONS: Taken together, we reveal the important role of miR-26a-5p in Cisplatin sensitivity and highlight its new mechanism in DNA damage and synthetic lethal.

Tracking tumor alteration in glioma through serum fibroblast activation protein combined with image.

PURPOSE: Detecting tumor progression of glioma continues to pose a formidable challenge. The role of fibroblast activation protein (FAP) in gliomas has been demonstrated to facilitate tumor progression. Glioma-circulating biomarkers have not yet been used in clinical practice. This study seeks to evaluate the feasibility of glioma detection through the utilization of a serum FAP marker. METHODS: We adopted enzyme-linked immunosorbent assay (ELISA) technique to quantify the relative FAP level of serum autoantibodies in a cohort of 87 gliomas. The correlation between preoperative serum autoantibody relative FAP levels and postoperative pathology, including molecular pathology was investigated. A series of FAP tests were conducted on 33 cases of malignant gliomas in order to ascertain their efficacy in monitoring the progression of the disease in relation to imaging observations. To validate the presence of FAP expression in tumors, immunohistochemistry was conducted on four gliomas employing a FAP-specific antibody. Additionally, the investigation encompassed the correlation between postoperative tumor burden, as assessed through volumetric analysis, and the relative FAP level of serum autoantibodies. RESULTS: A considerable proportion of gliomas exhibited a significantly increased level of serum autoantibody relative FAP level. This elevation was closely associated with both histopathology and molecular pathology, and demonstrated longitudinal fluctuations and variations corresponding to the progression of the disease The correlation between the rise in serum autoantibody relative FAP level and tumor progression and/or exacerbation of symptoms was observed. CONCLUSIONS: The measurement of serum autoantibody relative FAP level can be used to detect the disease as a valuable biomarker. The combined utilization of its detection alongside MR imaging has the potential to facilitate a more accurate and prompt diagnosis.

Effectiveness and safety of REBACIN as a non-invasive intervention for persistent high-risk human papillomavirus infection: A real-world prospective multicenter cohort study.

BACKGROUND: We previously reported that REBACIN effectively eliminates persistent high-risk human papillomavirus (hrHPV) infection. Here, we conducted a prospective multicenter cohort study to evaluate the safety and effectiveness of REBACIN, taking into account factors such as specific hrHPV subtype and patient's age. METHODS: According to inclusion/exclusion criteria and participant willingness, 3252 patients were divided into REBACIN group while 249 patients into control group. Patients in REBACIN group received one course treatment of intravaginal administration of REBACIN while no treatment in control group. After drug withdrawal, participants in both groups were followed up. RESULTS: The clearance rate of persistent hrHPV infection in REBACIN group was 60.64%, compared to 20.08% in control group. Specifically, the clearance rates for single-type infection of HPV16 or HPV18 were 70.62% and 69.23%, respectively, which was higher than that of HPV52 (59.04%) or HPV58 (62.64%). In addition, the single, double, and triple/triple+ infections had a clearance rate of 65.70%, 53.31%, and 38.30%, respectively. Moreover, 1635 patients under 40 years old had a clearance rate of 65.14%, while it was 55.08% for 1447 patients over 40 years old. No serious adverse effects were found. CONCLUSION: This study confirmed that REBACIN can effectively and safely eliminate persistent hrHPV infection, which the clearance rate of HPV16/18 is higher than that of HPV52/58, the clearance rate of single-type infection is higher than that of multiple-type infections, and the clearance rate in young patients is higher than that in elder patients, providing a guidance for REBACIN application in clearing hrHPV persistent infection in real-world settings. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Registration Number: ChiCTR1800015617 http://www.chictr.org.cn/showproj.aspx?proj=26529 Date of Registration: 2018-04-11.

LncRNA ZNF593-AS Alleviates Contractile Dysfunction in Dilated Cardiomyopathy.

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Zn(II) Coordination Polymer: Luminescence Sensing for Fe3+ Ion and Used as Metal Gel Particles Against Lung Cancer.

Presented here is a new Zn(II) coordination polymer, namely [Zn2(L)2(bpe)]n (1, H2L = 4-({2-[(4-carboxyphenoxy)methyl]phenyl}methoxy)benzoic acid, bpe = 1,2-bis(4-pyridinyl)ethane), which has been hydrothermally synthesized via the mixed-ligand strategy. Moreover, compound 1 emits intense luminescence at room temperature, and can be used as a luminescent sensor for the detection of Fe3+ in water solution with high selectivity and sensitivity. As representatives of natural polysaccharides, hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) have good biocompatibility. A new type of HA/CMCS gel particles loaded with Paclitaxel drug metal-organic framework was prepared by chemical synthesis method and its micromorphology was studied. Finally, biological experiments were conducted to evaluate the new system's effect on the activity of human lung cancer cells.

Effect of silencing CITED1 gene to regulate PI3K/AKT pathway on the biological function of PTC cells and its mechanism.

This study aims to investigate the effect of silencing the CITED1 gene to regulate the PI3K/AKT pathway on the biological function of papillary thyroid carcinoma (PTC) cells and its mechanism of action. Human PTC cells SW1736 were divided into 4 groups: control group, siCITED1 group, LY294002 group and siCITED1+LY294002 group. CITED1 was silenced by transfection with siCITED1 plasmid. The PI3K/AKT pathway was inhibited by LY294002 (5 µmmol/L). Each group was determined for cell proliferation, apoptosis and invasion capabilities, as well as PI3K/AKT transcription and protein expression levels. CITED1 mRNA and protein levels in the siCITED1 group and the siCITED1+LY294002 group were significantly lower than those in the control group (P < 0.05), and the two levels were not significantly different between the LY294002 group and the control group (P > 0.05). Compared with the control group, the siCITED1 group showed remarkably lower proliferation and invasion capabilities, and remarkably higher apoptosis rate (P < 0.05). There was no significant difference in proliferation, apoptosis and invasion capabilities between the LY294002 group and the siCITED1+LY294002 group (P > 0.05), both of which had significantly lower proliferation and invasion capabilities but significantly higher apoptosis rate than the siCITED1 group (P < 0.05). PI3K and AKT protein levels in the siCITED1 group were significantly lower than those in the control group (P < 0.05). The PI3K and AKT protein levels in the LY294002 group and the siCITED1+LY294002 group were not significantly different (P > 0.05), and were significantly lower than those in the siCITED1 group (P < 0.05). In conclusion: CITED1 silence may inhibit the progression of PTC cells by inhibiting the PI3K/AKT pathway.

Pirfenidone attenuates nonalcoholic fatty liver disease through activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway.

Nonalcoholic fatty liver disease (NAFLD) originates from the hepatopathy of fatty liver. Pirfenidone is a novel broad-spectrum anti-fibrosis agent used for treating various kinds of tissue fibrosis. The present study will evaluate the effects of Pirfenidone on liver injury in high-fat diet (HFD)-fed mice to evaluate the value of Pirfenidone in treating NAFLD. The pathology of NAFLD was simulated by feeding mice with an HFD in the present study, followed by treating the HFD mice with 150 and 300 mg/kg/day Pirfenidone once a day. The pathological state of HFD mice was identified by the elevated liver weight, promoted serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels, declined serum high-density lipoprotein cholesterol (HDL-C) levels, increased alanine aminotransferase and aspartate aminotransferase activity, and histopathological changes to the liver tissues, all of which were dramatically ameliorated by 150 and 300 mg/kg Pirfenidone administration. Furthermore, the excessive production of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and IL-6, as well as upregulated phosphorylated nuclear factor kappa-B (p- NF-κB p65), were observed in HFD-fed mice, but significantly reversed by Pirfenidone. Finally, activated oxidative stress, identified by promoted malondialdehyde (MDA) levels and declined catalase (CAT) activity, was observed in HFD-fed mice, accompanied by the downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and sterol-regulatory element-binding proteins-1c (SREBP-1c). After the treatment with Pirfenidone, oxidative stress was greatly mitigated. Our results imply that Pirfenidone ameliorated the progression of NAFLD by mediating inflammation and oxidative stress.

Design, synthesis, antiviral and fungicidal activities of novel polycarpine simplified analogues.

Fungal and viral diseases account for 70-80% of agricultural production losses caused by microbial diseases. Synthetic fungicides and antiviral agents have been used to treat plant diseases caused by plant pathogenic fungi and viruses, but their use has been criticized due to their adverse side effects. As alternative strategies, natural fungicides and antiviral agents have attracted many researchers' interest in recent years. Herein, we designed and synthesized a series of novel polycarpine simplified analogues. Antiviral activity research against tobacco mosaic virus (TMV) revealed that most of the designed compounds have good antiviral activities. The virucidal activities of 4, 6d, 6f, 6h, and 8c are higher than that of polycarpine and similar to that of ningnanmycin. The structure simplified compound 8c was selected for further antiviral mechanism research which showed that compound 8c could inhibit the formation of 20S protein discs by acting on TMV coat protein. These compounds also displayed broad-spectrum fungicidal activities against 7 kinds of plant fungi. This work lays the foundation for the application of polycarpine simplified analogues in crop protection.

Lung nodule pre-diagnosis and insertion path planning for chest CT images.

Medical image processing has proven to be effective and feasible for assisting oncologists in diagnosing lung, thyroid, and other cancers, especially at early stage. However, there is no reliable method for the recognition, screening, classification, and detection of nodules, and even deep learning-based methods have limitations. In this study, we mainly explored the automatic pre-diagnosis of lung nodules with the aim of accurately identifying nodules in chest CT images, regardless of the benign and malignant nodules, and the insertion path planning of suspected malignant nodules, used for further diagnosis by robotic-based biopsy puncture. The overall process included lung parenchyma segmentation, classification and pre-diagnosis, 3-D reconstruction and path planning, and experimental verification. First, accurate lung parenchyma segmentation in chest CT images was achieved using digital image processing technologies, such as adaptive gray threshold, connected area labeling, and mathematical morphological boundary repair. Multi-feature weight assignment was then adopted to establish a multi-level classification criterion to complete the classification and pre-diagnosis of pulmonary nodules. Next, 3-D reconstruction of lung regions was performed using voxelization, and on its basis, a feasible local optimal insertion path with an insertion point could be found by avoiding sternums and/or key tissues in terms of the needle-inserting path. Finally, CT images of 900 patients from Lung Image Database Consortium and Image Database Resource Initiative were chosen to verify the validity of pulmonary nodule diagnosis. Our previously designed surgical robotic system and a custom thoracic model were used to validate the effectiveness of the insertion path. This work can not only assist doctors in completing the pre-diagnosis of pulmonary nodules but also provide a reference for clinical biopsy puncture of suspected malignant nodules considered by doctors.

Surgical outcomes of basilar invagination type B without atlantoaxial dislocation through simple posterior fossa decompression: a retrospective study of 18 cases.

BACKGROUND: Basilar invagination (BI) is a common disease in the craniocervical junction (CVJ) area. Posterior fossa decompression with/without fixation is a controversial surgical strategy for BI type B. This study aimed to evaluate the efficacy of simple posterior fossa decompression in treating BI type B. METHODS: This study retrospectively enrolled BI type B patients who underwent simple posterior fossa decompression at Huashan Hospital, Fudan University between 2014.12 and 2021.12. Patient data and images were recorded pre- and postoperatively (at the last follow-up) to evaluate the surgical outcomes and craniocervical stability. RESULTS: A total of 18 BI type B patients (13 females), with a mean age of 44.2±7.9 years (range 37-62 years), were enrolled. The mean follow-up period was 47.7±20.6 months (range 10-81 months). All patients received simple posterior fossa decompression without any fixation. At the last follow-up, compared with preoperation, the JOA scores were significantly higher (14.2±1.5 vs. 9.9±2.0, p = 0.001); the CCA was improved (128.7±9.6° vs. 121.5±8.1° p = 0.001), and the DOCL was reduced (7.9±1.5 mm vs. 9.9±2.5 mm, p = 0.001). However, the follow-up and preoperative ADI, BAI, PR, and D/L ratio were similar. No patients had an unstable condition between the C1-2 facet joints that was observed in the follow-up CT and dynamic X-ray. CONCLUSIONS: In BI type B patients, simple posterior fossa decompression could improve neurological function and will not induce CVJ instability in BI type B patients. Simple posterior fossa decompression could be a satisfactory surgical strategy for BI type B patients, but preoperative CVJ stability assessment is crucial.

Overexpressed ZC3H13 suppresses papillary thyroid carcinoma growth through m6A modification-mediated IQGAP1 degradation.

PURPOSE: The purpose of this study was to clarify the effect of ZC3H13 on the growth of papillary thyroid carcinoma (PTC). METHODS: Firstly, we used qRT-PCR and Western blot to compare the difference in the expression of ZC3H13 between normal thyroid epithelial cells and PTC cell lines. Then, ZC3H13 overexpression/knockout thyroid cancer cells were constructed by lentivirus transfection, and the effects of overexpression of ZC3H13 on the proliferation, migration and invasion of PTC cells were detected by CCK8 and transwell experiments. Lastly, MeRIP-qPCR, RIP and o Actinomycin D were used to verify that ZC3H13 regulated the expression of downstream target gene IQGAP1 through m6A modification. RESULTS: ZC3H13 expression was decreased in PTC cell lines BCPAP, KTC-1, k1, HTH83, and TPC-1. Proliferation, invasion, and migration of PTC cells were inhibited by overexpressed ZC3H13 but increased by knockdown of ZC3H13. IQGAP1 expression was suppressed by ZC3H13 overexpression but enhanced by ZC3H13 knockdown. In ZC3H13-overexpressed PTC cells, the m6A level of IQGAP1 mRNA was increased, and the IQGAP1 mRNA expression was decreased with the increasing time of Actinomycin D treatment. YTHDF2 enriched more IQGAP1 mRNA than IgG and knockdown of YTHDF2 reversed the effect of ZC3H13 overexpression on IQGAP1 mRNA stability. The xenograft tumor experiment in nude mice confirmed that the overexpression of ZC3H13 inhibited tumor growth, while overexpression of IQGAP1 could reverse the inhibitory effect of ZC3H13 overexpression on tumor growth. CONCLUSION: ZC3H13 mediates IQGAP1 mRNA degradation by promoting m6A modification of IQGAP1 mRNA, this provides a prospective therapeutic target for PTC.