BACKGROUND: Compared with dural arteriovenous fistulas (DAVFs) in adult, paediatric DAVFs are notable for distinct clinical manifestations, low cure rate and poor prognosis. However, due to the limitations of small sample sizes, the long-term prognosis and follow-up data have not been described. METHODS: Clinical data from 43 consecutive paediatric DAVFs were documented and analysed between 2002 and 2022 at the author's institution. They were divided into infantile (Lasjaunias classification) and non-infantile (adult type and dural sinus malformation (DSM)) type DAVFs based on prognosis differences. RESULTS: Their mean age at first symptoms was 8.4±6.0 years. 29 boys and 14 girls presented between at birth and 18 years of age. 5 of 10 patients ≤1 year of age presented with asymptomatic cardiomegaly compared with 5/33 patients >1 year of age (p=0.022). 42 (88.4%) patients received endovascular treatment alone, while 9.3% underwent radiosurgery, burr hole embolisation or surgery. 28 (65.1%) patients experienced DAVF obliteration by the end of treatment. Among them, 26 cases underwent embolisation alone, one case had embolisation in conjunction with surgery, and one case underwent burr hole embolisation. The overall complication rate among patients was 9.3%, all resulting from endovascular treatment. According to the Lasjaunias Classification, there were 18 cases of adult type, 17 cases of infantile type and 8 cases of DSM. Compared with non-infantile-type DAVFs, infantile-type DAVFs showed more times of treatment, lower cure rate and worse prognosis (p<0.001, 0.003 and 0.021, respectively). The average follow-up duration was 41.4±36.2 months (3-228 months). 8 (22.9%) patients died. CONCLUSIONS: Most adult-type DAVFs and DSMs can now be effectively treated with embolisation, resulting in good outcomes and prognosis. However, there are still challenges in treating infantile-type DAVFs, and the prognosis is frequently poor.
Nonlinear optical activities, especially second harmonic generation (SHG), are key phenomena in inversion-symmetry-broken two-dimensional (2D) transition metal dichalcogenides (TMDCs). On the other hand, anisotropic nonlinear optical processes are important for unique applications in nano-nonlinear photonic devices with polarization functions, having become one of focused research topics in the field of nonlinear photonics. However, the strong nonlinearity and strong optical anisotropy do not exist simultaneously in common 2D materials. Here, we demonstrate strong second-order and third-order susceptibilities of 64 pm/V and 6.2×10-19 m2/V2, respectively, in the even-layer PdPSe, which has not been discovered in other common TMDCs (e.g., MoS2). Strikingly, it also simultaneously exhibited strong SHG anisotropy with an anisotropic ratio of ~45, which is the largest reported among all 2D materials to date, to the best of our knowledge. In addition, the SHG anisotropy ratio can be harnessed from 0.12 to 45 (375 times) by varying the excitation wavelength due to the dispersion of χ ( 2 ) values. As an illustrative example, we further demonstrate polarized SHG imaging for potential applications in crystal orientation identification and polarization-dependent spatial encoding. These findings in 2D PdPSe are promising for nonlinear nanophotonic and optoelectronic applications.
Cordyceps cicadae (Hypocreales: Cordycipitaceae) is a renowned entomopathogenic fungus used as herbal medicine in China. However, wild C. cicadae resources have been threatened by heavy harvesting. We hypothesised that Bombyx mori L. (Lepidoptera: Bombycidae) could be a new alternative to cultivate C. cicadae due to the low cost of rearing. Bacterial communities are crucial for the formation of Cordyceps and for promoting the production of metabolites. To better understand the bacterial community structure associated with Cordyceps, three Claviciptaceae fungi were used to explore the pathogenicity of the silkworms. Here, fifth-instar silkworms were infected with C. cicadae, Cordyceps cateniannulata (Hypocreales: Cordycipitaceae) and Beauveria bassiana (Hypocreales: Cordycipitaceae). Subsequently, we applied high-throughput sequencing to explore the composition of bacterial communities in silkworms. Our results showed that all three fungi were highly pathogenic to silkworms, which suggests that silkworms have the potential to cultivate Cordyceps. After fungal infection, the diversity of bacterial communities in silkworms decreased significantly, and the abundance of Staphylococcus increased in mummified larvae, which may play a role in the death process when the host suffers infection by entomopathogenic fungi. Furthermore, there were high similarities in the bacterial community composition and function in the C. cicadae and C. cateniannulata infected samples, and the phylogenetic analysis suggested that these similarities may be related to the fungal phylogenetic relationship. Our findings reveal that infection with different entomopathogenic fungi affects the composition and function of bacterial communities in silkworms and that the bacterial species associated with Cordyceps are primarily host dependent, while fungal infection affects bacterial abundance.
Alcoholic fatty liver disease (FALD) and non-alcoholic fatty liver disease (NAFLD) have similar pathological spectra, both of which are associated with a series of symptoms, including steatosis, inflammation, and fibrosis. These clinical manifestations are caused by hepatic lipid synthesis and metabolism dysregulation and affect human health. Despite having been studied extensively, targeted therapies remain elusive. The Cytochrome P450 (CYP450) family is the most important drug-metabolising enzyme in the body, primarily in the liver. It is responsible for the metabolism of endogenous and exogenous compounds, completing biological transformation. This process is relevant to the occurrence and development of AFLD and NAFLD. In this review, the correlation between CYP450 and liver lipid metabolic diseases is summarised, providing new insights for the treatment of AFLD and NAFLD.
BACKGROUND: Congenital heart disease (CHD) is a leading cause of birth defect-related mortality. However, more recent CHD mortality data for China are lacking. Additionally, limited studies have evaluated sex, rural-urban, and region-specific disparities of CHD mortality in China. METHODS: We designed a population-based study using data from the Dataset of National Mortality Surveillance in China between 2008 and 2021. We calculated age-adjusted CHD mortality using the sixth census data of China in 2010 as the standard population. We assessed the temporal trends in CHD mortality by age, sex, area, and region from 2008 to 2021 using the joinpoint regression model. RESULTS: From 2008 to 2021, 33,534 deaths were attributed to CHD. The period witnessed a two-fold decrease in the age-adjusted CHD mortality from 1.61 to 0.76 per 100,000 persons (average annual percent change [AAPC] = -5.90%). Females tended to have lower age-adjusted CHD mortality than males, but with a similar decline rate from 2008 to 2021 (females: AAPC = -6.15%; males: AAPC = -5.84%). Similar AAPC values were observed among people living in urban (AAPC = -6.64%) and rural (AAPC = -6.12%) areas. Eastern regions experienced a more pronounced decrease in the age-adjusted CHD mortality (AAPC = -7.86%) than central (AAPC = -5.83%) and western regions (AAPC = -3.71%) between 2008 and 2021. Approximately half of the deaths (46.19%) due to CHD occurred during infancy. The CHD mortality rates in 2021 were lower than those in 2008 for people aged 0-39 years, with the largest decrease observed among children aged 1-4 years (AAPC = -8.26%), followed by infants (AAPC = -7.01%). CONCLUSIONS: CHD mortality in China has dramatically decreased from 2008 to 2021. The slower decrease in CHD mortality in the central and western regions than in the eastern regions suggested that public health policymakers should pay more attention to health resources and health education for central and western regions.
Autosomal dominant polycystic kidney disease (ADPKD) is commonly caused by PKD1, and mosaic PKD1 variants result in milder phenotypes. We present the case of a 32 year-old male with chronic active Epstein-Barr virus who underwent bone marrow transplantation with chemoradiotherapy at age 9. Despite a low-frequency mosaic splicing PKD1 variant, he developed severe renal cysts and end-stage renal disease in his 30 s. This case highlights how environmental factors may contribute to the genetic predisposition to ADPKD.
On-chip acousto-optic modulators that operate at an optical wavelength of 780 nm and a microwave frequency of 6.835 GHz are proposed. The modulators are based on a lithium-niobate-on-sapphire platform and efficiently excite surface acoustic waves and exhibit strong interactions with tightly confined optical modes in waveguides. In particular, a high-efficiency phase modulator and single-sideband mode converter are designed. We found that for both microwave and optical wavelengths below 1 µm, the interactions at the cross-sections of photonic waveguides are sensitive to the waveguide width and are significantly different from those in previous studies. Our designed devices have small footprints and high efficiencies, making them suitable for controlling rubidium atoms and realizing hybrid photonic-atomic chips. Furthermore, our devices have the potential to extend the acousto-optic modulators to other visible wavelengths for other atom transitions and for visible light applications, including imaging and sensing.
OBJECTIVE: The etiology, clinical presentation, diagnosis, and treatment strategies of chronic pancreatitis (CP) vary significantly between countries. Specifically, the etiology and surgical approaches to treating CP differ between China and Western countries. Therefore, this study aims to compare the disparities in CP profiles and management based on our single-center experience and recent data from the West. METHODS: From January 2007 to December 2017, a total of 130 consecutive patients with histologically confirmed chronic pancreatitis (CP) underwent surgical treatment at the First Affiliated Hospital of Nanjing Medical University. The clinical features, etiology, risk factors, and operative procedures of these CP patients were analyzed and compared with recent data from Western countries. RESULTS: Our patient cohort was predominantly male (3.19:1), with a median age of 50.2 ± 9.8 years. Upper abdominal pain was the most common symptom, present in 102 patients (78.5%). The most common etiology was obstructive factors (47.7%), followed by alcohol (34.6%). The incidence of genic mutation was 2%, significantly lower than rates reported in Western research. Steatorrhea, weight loss, and jaundice were present in 6.9%, 18.5%, and 17.7% of patients, respectively. Pancreatic cysts or pseudocysts were diagnosed in 7 patients (5.4%). The following procedures were performed: Partington procedure in 33 patients (25.4%), Frey procedure in 17 patients (13.2%), Berne procedure in 5 patients (3.9%), Beger procedure in 1 patient (0.8%), pancreaticoduodenectomy in 17 patients (13.1%), pylorus-preserving pancreaticoduodenectomy in 18 patients (13.9%), middle pancreatectomy in 1 patient (0.8%), and distal pancreatectomy in 9 patients (6.9%). Choledochojejunostomy was performed in 14 patients (10.8%), gastroenterostomy in 2 (1.5%), and 15 patients (11.5%) underwent aspiration biopsy. CONCLUSION: Our study confirms that, etiologically, obstructive chronic pancreatitis (CP) is more frequent in the Chinese population than in Western populations. Although diagnostic instruments and operative procedures in China and Western countries are roughly comparable, slight differences exist in relation to diagnostic flowcharts/criteria and the indications and optimal timing of surgery.
Pancreatitis, Chronic , Humans , Male , Adult , Middle Aged , Female , Pancreatitis, Chronic/diagnosis , Pancreatitis, Chronic/epidemiology , Pancreatitis, Chronic/etiology , Pancreaticoduodenectomy/methods , Pancreatectomy/methods , Risk Factors , China/epidemiology , Treatment Outcome
A series of NH2-functionalized nano-sized magnetic metal-organic frameworks (MOFs) were prepared in this study for Cr(VI) removal from wastewater. It was observed that not only the morphological, i.e., orientation growth of N-doped and iron-based metal-organic frameworks, but also the adsorption of magnetic MOFs is largely related to the used amount of ammonium hydroxide in preparation. For example, with increasing amounts of ammonium hydroxide used in preparation, the morphology of magnetic MOFs changed from spherical to cube and triangular cone. Moreover, the maximum adsorption capacity of spherical-magnetic MOFs, cubic-magnetic MOFs and triangular cone-magnetic MOFs could be up to 204.08 mg/g, 232.56 mg/g and 270.27 mg/g, respectively. Under optimal conditions, the adsorption process of magnetic MOFs for Cr(VI) was consistent with the pseudo-second-order rate equation (R2 = 1) and Langmuir isotherm model (R2 > 0.99). Therefore, magnetic MOFs developed in this work offered a viable option for the removal of Cr(VI) from wastewater.
AIMS: Primary mucoepidermoid carcinomas (MECs) of the sinonasal tract and nasopharynx are rare entities that represent a diagnostic challenge, especially in biopsy samples. Herein, we present a case series of MECs of the sinonasal and skull base and its mimics to evaluate the clinicopathological and molecular characteristics in order to avoid misdiagnosis. METHODS: We reviewed the pathology records of patients diagnosed from 2014 to 2022. Thirty MECs were consecutively diagnosed during that period. RESULTS: Based on morphological and fluorescence in situ hybridization (FISH) analyses, 30 tumors originally diagnosed as MECs were separated into MAML2 fusion-positive (7 cases) and MAML2 fusion-negative groups (23 cases), in which 14 tumors were positive for the EWSR1::ATF1 fusion; these tumors were reclassified to have hyalinizing clear cell carcinoma (HCCC). The remaining nine MAML2 FISH negative cases were reconfirmed as squamous cell carcinoma (SCC, 3 cases) which showed keratinization and high Ki-67 expression; DEK::AFF2 carcinomas (2 cases), in which DEK gene rearrangement was detected by FISH; and MECs as previously described (4 cases) with typical morphological features. Including 7 MAML2 rearrangements tumors, 11 MEC cases had a male-to-female ratio of 4.5:1, and 6 tumors arose from the nasopharyngeal region, while 5 tumors arose from the sinonasal region. The prognosis of this series of salivary gland-type MECs was favorable. CONCLUSIONS: Our study confirmed that HCCC runs the risk of being misdiagnosed as MEC in the sinonasal tract and nasopharynx, particularly with biopsy specimens. Careful histological evaluation with supporting molecular testing can facilitate pathological diagnoses.
Carcinoma, Mucoepidermoid , Carcinoma, Squamous Cell , Salivary Gland Neoplasms , Humans , Male , Female , Carcinoma, Mucoepidermoid/diagnosis , Carcinoma, Mucoepidermoid/genetics , Carcinoma, Mucoepidermoid/pathology , In Situ Hybridization, Fluorescence , Transcription Factors/genetics , Salivary Gland Neoplasms/pathology
OBJECTIVE: Isolated spinal aneurysms (ISAs) are rare causes of subarachnoid hemorrhage (SAH), which encompass a highly heterogeneous group of clinical entities with multifarious pathogeneses, clinical characteristics, and treatment strategies. Therefore, knowledge about the ISAs remains inadequate. In this study, the authors present a comprehensive analysis of clinical data associated with ISAs at their institutions to enhance the understanding of this disease. METHODS: Patients with ISAs confirmed by spinal angiography or surgery at the authors' institutions between 2015 and 2022 were included. Data regarding clinical presentation, lesion location, aneurysm morphology, comorbidities, treatment results, and clinical outcomes were reviewed. RESULTS: Seven patients with ISAs were included in the study. Among them, 4 patients (57.1%) experienced severe headache, and 3 patients (42.9%) reported sudden-onset back pain. Additionally, lower-extremity weakness and urinary retention were observed in 2 of these patients (28.6%). Four of the aneurysms exhibited fusiform morphology, whereas the remaining were saccular. All saccular aneurysms in this series were attributed to hemodynamic factors. Conservative treatment was administered to 3 patients, 2 of whom underwent follow-up digital subtraction angiography, which showed spontaneous occlusion of both aneurysms. Four patients ultimately underwent invasive treatments, including 2 who underwent microsurgery and 2 who received endovascular embolization. One patient died of recurrent SAH, while the remaining 6 patients had a favorable prognosis at the latest follow-up assessment. CONCLUSIONS: The morphology of aneurysms may be associated with their etiology. Saccular ISAs are usually caused by pressure due to abnormally increased blood flow, whereas fusiform lesions may be more likely to be secondary to vessel wall damage. The authors found that a saccular spinal aneurysm in young patients with a significant dilated parent artery may be a vestige of spinal cord arteriovenous shunts. ISAs can be managed by surgical, endovascular, or conservative procedures, and the clinical outcome is generally favorable. However, the heterogeneous nature of the disease necessitates personalized treatment decision-making based on specific clinical features of each patient.
Embolization, Therapeutic , Humans , Male , Female , Middle Aged , Adult , Aged , Treatment Outcome , Subarachnoid Hemorrhage/etiology , Subarachnoid Hemorrhage/surgery , Subarachnoid Hemorrhage/therapy , Aneurysm/surgery , Aneurysm/etiology , Aneurysm/diagnostic imaging , Retrospective Studies , Microsurgery , Angiography, Digital Subtraction , Endovascular Procedures , Spinal Cord/blood supply , Spinal Cord/pathology
BACKGROUND: Isolated sinus dural arteriovenous fistulas (DAVFs) constitute a rare and distinctive subtype of DAVF, typically found in small case numbers or case reports. The optimal treatment for this DAVF type remains unclear. OBJECTIVE: This study aims to further detail the treatment outcomes of isolated sinus DAVFs in a sizable cohort from a single center. METHODS: A retrospective study was undertaken on a consecutive series of patients with isolated sinus DAVFs treated at a single institution from 2002 to 2022. The article delineates the clinical presentation, angiographic features, treatment strategy, clinical and angiographic outcomes, and complications. RESULTS: The cohort consisted of 31 males and 13 females, with an average age of 52.0 ± 15.5 years (range, 16-83). The success rate for trans-arterial embolization (TAE) was 97.3% (36/37). Transvenous embolization (TVE) with the reopening technique was successful in 3 of 4 patients (75.0%). Two open burr-hole TVE cases (66.7%, 2/3) and one surgery (100%) resulted in immediate complete closure of the fistula. Immediate complete occlusion was achieved in 93.2% (41/44) of cases. There was one major complication (2.3%, 1/44) and two fistulas recurred (9.5%, 2/21). CONCLUSIONS: The majority of isolated sinus DAVFs can be effectively treated with TAE using Onyx. TVE and surgery serve as alternative techniques when arterial access is deemed inappropriate or when complete occlusion cannot be attained with TAE. Complete embolization of isolated sinus DAVFs by TAE can typically be achieved without delay.
Central Nervous System Vascular Malformations , Embolization, Therapeutic , Male , Female , Humans , Adult , Middle Aged , Aged , Retrospective Studies , Treatment Outcome , Central Nervous System Vascular Malformations/diagnostic imaging , Central Nervous System Vascular Malformations/surgery , Vascular Surgical Procedures , Angiography , Embolization, Therapeutic/adverse effects
RNA-binding proteins (RBPs) interact with RNA and ubiquitously regulate RNA transcripts during their life cycle, playing a fundamental role in the progression of angiogenesis-related diseases. In the skeletal system, endothelium-dependent angiogenesis is indispensable for bone formation. However, the role of RBPs in endothelium-dependent bone formation is unclear. Here, we show that RBP-Y-box-binding protein 1 (YBX1) was strongly reduced in the bone vasculature of ovariectomy (OVX) mice. Endothelial cell-specific deletion of Ybx1 impaired CD31-high, endomucin-high (CD31hiEMCNhi) endothelium morphology and resulted in low bone mass whereas Ybx1 overexpression promoted angiogenesis-dependent osteogenesis and ameliorated bone loss. Mechanistically, YBX1 deletion disrupted CD31, EMCN, and bone morphogenetic protein 4 (BMP4) stability in an m5C-dependent manner and blocked endothelium-derived BMP4 release, thereby inhibiting osteogenic differentiation of bone mesenchymal stromal cells. Administration of recombinant BMP4 protein restored impaired bone formation in Ybx1 deletion mice. Tail vein injection of CD31-modified polyethylene glycol-poly (lactic-co-glycolic acid) carrying sciadopitysin, a natural YBX1 agonist, pharmacologically partially reversed CD31hiEMCNhi vessels' decline and improved bone mass in both OVX and aging animals. These findings demonstrated the role of RBP-YBX1 in angiogenesis-dependent bone formation and provided a therapeutic approach for ameliorating osteoporosis.
Osteogenesis , Osteoporosis , Transcription Factors , Animals , Female , Mice , Bone and Bones/metabolism , Endothelium/metabolism , Osteogenesis/physiology , Osteoporosis/genetics , RNA , Transcription Factors/genetics
Myxofibrosarcoma (MFS) is a malignant fibroblastic/myofibroblastic neoplasm with a prominent myxoid area. It has the clinical features of frequent local recurrence (LR) and occasional distant metastasis. Robust epidemiological data on MFS in China are lacking. The aim of this retrospective analysis was to determine the natural history of MFS, identify prognostic factors for recurrence and describe the real-life outcomes of MFS. We reviewed 52 patients with primary MFS from the First Affiliated Hospital of Nanjing Medical University diagnosed between 2016 and 2020. All tumors were subjected to retrospective univariate analysis for prognostic factors of the disease, including tumor size, grade, location and sex; patient age; planned operation; surgical margin; and laboratory results. The significant factors identified by univariate analysis were subsequently analyzed via multivariate analysis. Overall survival (OS), post-treatment LR and metastatic-free survival were assessed as outcomes. The median age was 61 years (range, 13-93). Fourteen (26.92%) patients exhibited low grade disease, and 38 (73.08%) exhibited high grade disease. Among the 29 males, and 23 females, 15 (28.85%) had tumors in the trunk, 37 (71.15%) had tumors in the extremities, 26 had undergone planned surgery, and 26 had unexpected unplanned operation. The margin was negative in 39 (75%) patients and positive in 13 patients (25%). The serum creatine kinase (CK) concentration was high level in 33 (63.46%) patients and low level in 19 (36.54%) patients. The serum lactate dehydrogenase (LDH) levels were low in 23 (44.23%) patients and high in 29 (55.77%) patients. LR was observed in 25 patients (48.08%), and 4 patients developed metastasis. A worse LR rate was found for patients with a low CK level (84.21%) than for those with a high CK level (27.27%) at 5 years (p < 0.05). The LR rate of patients who underwent planned surgery was lower than that of patients who underwent unplanned surgery (p < 0.05). There were significantly more patients with positive margins than patients with negative margins (92.30%, and 33.33%, respectively; p < 0.05). Moreover, superficial tumors were also associated with greater recurrence rate (2/20 [10%]) than deep tumors, (23/32 [71.86%]) [p < 0.05]. The probability of LR in patients with MFS was significantly greater in association with unplanned operations, positive margins, low serum CK levels or superficial tumor depth. These data could help identify high-risk patients; thus, more careful follow-up should be performed for higher-risk patients. Diagnosis and treatment at qualified regular medical centers can reduce the local recurrence rate of MFS.
Fibrosarcoma , Histiocytoma, Malignant Fibrous , Male , Female , Adult , Humans , Middle Aged , Retrospective Studies , Fibrosarcoma/surgery , Fibrosarcoma/pathology , Extremities/pathology , Prognosis , Histiocytoma, Malignant Fibrous/pathology , Neoplasm Recurrence, Local/pathology
BACKGROUND AND OBJECTIVES: Intraorbital arteriovenous fistulas (AVFs) are an extremely rare subtype of intracranial fistula with ophthalmic symptoms similar to cavernous sinus dural AVFs or carotid cavernous fistulas but worse visual outcomes. Here, we present a case series and thorough systematic review on intraorbital AVFs to demonstrate treatment modalities and address this rare type of AVF. METHODS: We conducted a retrospective study at a single center, in which we identified all cases of intraorbital AVFs that occurred between 2002 and 2022. We collected and analyzed data on demographics, fistula characteristics, treatment methods, clinical outcomes, and fistula closure. In addition, we conducted a systematic review of intraorbital AVFs. RESULTS: Seven cases in our center and 41 cases of intraorbital AVFs reported in the 35 articles were identified. At our center, transarterial embolization (TAE) (42.9%) alone resulted in immediate complete occlusion in 3 cases. Transvenous embolization (14.3%) resulted in one case of immediate complete occlusion. In 2 cases, surgery (28.6%) resulted in immediate complete occlusion. In one case, conservative treatment (14.3%) was used, and the fistula was eventually spontaneously occluded. Immediate complete occlusion rate was 85.7%. One blindness occurred (14.3%). In the literature reported, 3 cases (60%) of retinal artery occlusion were reported when performing TAE via the ophthalmic artery. Two fistulas recurred as reported. In 33 (80.5%) patients, the fistula was finally completely occluded. CONCLUSION: TAE via the ophthalmic artery carries a high risk of blindness and a low cure rate. Transvenous techniques such as conventional transvenous routes, surgical exposure, or direct puncture of the drainage vein have been used as the first line of treatment for intraorbital AVFs.
Three new griseofulvin derivatives, griseofulvinoside A-C (1-3), were isolated from the ethyl acetate extract of the solid fermentation product of Aureobasidium pullulans. Their structures were elucidated based on extensive spectroscopic data analysis of MS, 1D and 2D NMR. The antifungal activities of new compounds were evaluated against four phytopathogenic fungi in vitro, and all test compounds demonstrated inhibitory effects. Among them, compound 2 exhibited the most potent activities against the four selected phytopathogenic fungi with inhibitory rates ranging from 40.2 to 75.8% at 0.2 mg/mL.
The role of RNA methyltransferase 3 (METTL3) in tumor progression when tethered to aberrantly expressed oncogenes remains unknown. In especial, the correlation between cervical cancer (CCa)-derived exosomes and m6A methylation in malignant traits of cervical epithelium is currently elusive. Mortalin expression was found to be up-regulated in plasma exosomes isolated from CCa patients. Furthermore, mortalin gained increased mRNA stability and enhanced translation efficiency via the m6A methylation in the HSPA9 mRNA 3'UTR, which was catalysed by METTL3 in CCa cells. Exosomal mortalin overexpression significantly promoted the proliferation, migration and invasion of CCa both in vitro and in vivo. Additionally, exosome-encapsulated mortalin suppressed cellular senescence and facilitated malignant transformation by blocking nuclear transport of p53, thereby preventing the p53-Gadd45A interaction and resulting in inactivation of p53. Our studies demonstrated the significant role of METTL3 mediated exosomal mortalin in malignant transformation and cellular senescence suppression of CCa. Exosomal mortalin could clinically serve as a potential early-diagnosis biomarker and therapeutic target for CCa given its abundance and propensity to be found.
Adenine/analogs & derivatives , Methyltransferases , Uterine Cervical Neoplasms , Female , Humans , Methyltransferases/genetics , Methyltransferases/metabolism , Uterine Cervical Neoplasms/genetics , Tumor Suppressor Protein p53/genetics , Cell Transformation, Neoplastic , Cellular Senescence , HSP70 Heat-Shock Proteins/genetics , HSP70 Heat-Shock Proteins/metabolism , Mitochondrial Proteins/metabolism
BACKGROUND: Metastasis has emerged as the major reason of treatment failure and mortality in patients with nasopharyngeal carcinoma (NPC). Growing evidence links abnormal DNA methylation to the initiation and progression of NPC. However, the precise regulatory mechanism behind these processes remains poorly understood. METHODS: Bisulfite pyrosequencing, RT-qPCR, western blot, and immunohistochemistry were used to test the methylation and expression level of NEURL3 and its clinical significance. The biological function of NEURL3 was examined both in vitro and in vivo. Mass spectrometry, co-immunohistochemistry, immunofluorescence staining, and ubiquitin assays were performed to explore the regulatory mechanism of NEURL3. RESULTS: The promoter region of NEURL3, encoding an E3 ubiquitin ligase, was obviously hypermethylated, leading to its downregulated expression in NPC. Clinically, NPC patients with a low NEURL3 expression indicated an unfavorable prognosis and were prone to develop distant metastasis. Overexpression of NEURL3 could suppress the epithelial mesenchymal transition and metastasis of NPC cells in vitro and in vivo. Mechanistically, NEURL3 promoted Vimentin degradation by increasing its K48-linked polyubiquitination at lysine 97. Specifically, the restoration of Vimentin expression could fully reverse the tumor suppressive effect of NEURL3 overexpression in NPC cells. CONCLUSIONS: Collectively, our study uncovers a novel mechanism by which NEURL3 inhibits NPC metastasis, thereby providing a promising therapeutic target for NPC treatment.
Nasopharyngeal Neoplasms , Ubiquitin-Protein Ligases , Humans , Nasopharyngeal Carcinoma/genetics , Ubiquitin-Protein Ligases/genetics , Vimentin/genetics , Epithelial-Mesenchymal Transition , Nasopharyngeal Neoplasms/genetics
BACKGROUND: Arteriovenous shunt below the conus medullaris (AVS-BC) is easily misdiagnosed and mistreated due to its rarity. Achieving an anatomical cure solely through endovascular or surgical means is challenging. This study aimed to summarize the clinical and radiological features of AVS-BC and evaluate the safety and efficacy of hybrid techniques represented by intraoperative direct venous puncture and embolization (IVPE). METHODS: The patients with AVS-BC were grouped into those with dural, intradural, and paravertebral shunts. The patients undergoing hybrid procedures were consecutively recruited between August 2016 and July 2022. The modified Aminoff and Logue's Scale (mALS) and the modified Denis Pain and Numbness Scale (mDS) were used to evaluate motor and sensation disturbances. RESULTS: A total of 42 patients (35 males, 83.3%) were included with an average age of 57.38±10.79 years. Most patients presented with lower limb weakness and sphincter disturbances. Their preoperative average mALS score was 7.17±2.61 and the preoperative average mDS score was 3.88±1.76. There were 28 patients (66.7%) who received IVPE. The mean clinical follow-up reached 41.30±21.10 months. All patients achieved anatomical cures without permanent neurological complications. It showed a significant improvement in mALS scores after the intervention in the spinal dural arteriovenous fistula only (P=0.026). No recurrences were reported. CONCLUSIONS: Differentiating AVS-BC mainly relied on identifying supplying arteries, shunt placements, and draining veins. The hybrid technique typified by IVPE conferred a safe anatomical cure for AVS-BC.
Magnetic-free nonreciprocal optical devices have attracted great attention in recent years. Here, we investigated the magnetic-free polarization rotation of light in an atom vapor cell. Two mechanisms of magnetic-free nonreciprocity have been realized in ensembles of hot atoms, including electromagnetically induced transparency and optically-induced magnetization. For a linearly polarized input probe light, a rotation angle up to 86.4° has been realized with external control and pump laser powers of 10â mW and is mainly attributed to the optically-induced magnetization effect. Our demonstration offers a new approach to realize nonreciprocal devices, which can be applied to solid-state atom ensembles and may be useful in photonic integrated circuits.
