ABSTRACT
The dysregulation of N6-methyladenosine (m6A) RNA modification is widely recognized for its crucial roles in various diseases, including pulmonary hypertension (PH). Prior studies have highlighted the significant role of METTL3 in the pathogenesis of PH. Nevertheless, the potential and underlying mechanisms of METTL3 and its inhibitors as targets for PH treatment require further elucidation. In this study, we observed increased levels of METTL3 in various rodent models of PH. In vitro studies revealed that METTL3 silencing or treatment with STM2457, a specific METTL3 inhibitor, attenuated the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) stimulated by platelet-derived growth factor-BB (PDGF-BB) or hypoxia. Moreover, in vivo experiments using AAV9-mediated METTL3 silencing or STM2457 inhibition demonstrated improvement in SU5416/hypoxia-induced PH in mice. Additionally, m6A RNA immunoprecipitation analysis identified RBPJ as a gene regulated by METTL3 in rodent models of PH. Loss-of-function studies showed that silencing RBPJ could attenuate the changes in the proliferation and migration of PASMCs induced by PDGF-BB or hypoxia. Further studies indicated that METTL3 and YTHDF1 regulate RBPJ mRNA expression in an m6A-dependent manner. These findings indicated that targeting METTL3 may be a promising therapeutic strategy for treating PH, and modulation of RBPJ could offer a potential intervention mechanism.
ABSTRACT
Structural variants (SVs) of unknown significance are great challenges for prenatal risk assessment, especially when involving dose-sensitive genes such as DMD The pathogenicities of 5'-terminal DMD duplications in the database remain controversial. Four prenatal cases with Xp21.1 duplications were identified by routine prenatal genomic testing, encompassing the 5'-UTR to exons 1-2 in family 1 and family 2, and to exons 1-9 in family 3. The duplication in family 4 was non-contiguous covering the 5'-UTR to exon 1 and exons 3-7. All were traced to unaffected males in the family pedigrees. A new genome-wide approach of optical genome mapping was performed in families 1, 2, and 3 to delineate the breakpoints and orientation of the duplicated fragments. The extra copies were tandemly inserted into the upstream of DMD, preserving the integrity of ORF from the second copy. The pathogenicities were thus reclassified as likely benign. Our data highlight the importance of structural delineation by optical genome mapping in prenatal risk assessment of incidentally identified SVs involving DMD and other similar large dose-sensitive genes.
Subject(s)
Dystrophin , Pedigree , Humans , Female , Male , Risk Assessment/methods , Pregnancy , Dystrophin/genetics , Prenatal Diagnosis/methods , Chromosome Mapping/methods , Chromosomes, Human, X/genetics , Muscular Dystrophy, Duchenne/genetics , Muscular Dystrophy, Duchenne/diagnosis , Chromosome Duplication/genetics , Exons/genetics , Gene Duplication/genetics , AdultABSTRACT
Ten new drimane meroterpenoids talarines A-J (1-10), along with six known analogues (11-16), were isolated from desert soil-derived fungus Talaromyces pinophilus LD-7. Their 2D structures were elucidated by comprehensive interpretation of NMR and HRESIMS data. Electronic circular dichroism calculation was used to establish their absolute configurations. Compounds 2, 10, and 11 showed antiviral activities toward vesicular stomatitis virus with IC50 values of 18, 15, and 23 nM, respectively. The structure-bioactivity relationship indicated that chlorine substitution at C-5 contributed greatly to their antiviral activities. Finally, we identified a new halogenase outside the biosynthetic gene cluster, which was responsible for C-5 halogenation of the precursor isocoumarin 17 as a tailoring step in chlorinated meroterpenoids assembly.
Subject(s)
Antiviral Agents , Talaromyces , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/isolation & purification , Biosynthetic Pathways , Halogenation , Molecular Structure , Polycyclic Sesquiterpenes/pharmacology , Structure-Activity Relationship , Talaromyces/chemistry , Terpenes/pharmacology , Terpenes/chemistry , Terpenes/isolation & purificationABSTRACT
Low-dose computed tomography (LDCT) denoising tasks face significant challenges in practical imaging scenarios. Supervised methods encounter difficulties in real-world scenarios as there are no paired data for training. Moreover, when applied to datasets with varying noise patterns, these methods may experience decreased performance owing to the domain gap. Conversely, unsupervised methods do not require paired data and can be directly trained on real-world data. However, they often exhibit inferior performance compared to supervised methods. To address this issue, it is necessary to leverage the strengths of these supervised and unsupervised methods. In this paper, we propose a novel domain adaptive noise reduction framework (DANRF), which integrates both knowledge transfer and style generalization learning to effectively tackle the domain gap problem. Specifically, an iterative knowledge transfer method with knowledge distillation is selected to train the target model using unlabeled target data and a pre-trained source model trained with paired simulation data. Meanwhile, we introduce the mean teacher mechanism to update the source model, enabling it to adapt to the target domain. Furthermore, an iterative style generalization learning process is also designed to enrich the style diversity of the training dataset. We evaluate the performance of our approach through experiments conducted on multi-source datasets. The results demonstrate the feasibility and effectiveness of our proposed DANRF model in multi-source LDCT image processing tasks. Given its hybrid nature, which combines the advantages of supervised and unsupervised learning, and its ability to bridge domain gaps, our approach is well-suited for improving practical low-dose CT imaging in clinical settings. Code for our proposed approach is publicly available at https://github.com/tyfeiii/DANRF.
ABSTRACT
Low-dose computed tomography (LDCT) has gained increasing attention owing to its crucial role in reducing radiation exposure in patients. However, LDCT-reconstructed images often suffer from significant noise and artifacts, negatively impacting the radiologists' ability to accurately diagnose. To address this issue, many studies have focused on denoising LDCT images using deep learning (DL) methods. However, these DL-based denoising methods have been hindered by the highly variable feature distribution of LDCT data from different imaging sources, which adversely affects the performance of current denoising models. In this study, we propose a parallel processing model, the multi-encoder deep feature transformation network (MDFTN), which is designed to enhance the performance of LDCT imaging for multisource data. Unlike traditional network structures, which rely on continual learning to process multitask data, the approach can simultaneously handle LDCT images within a unified framework from various imaging sources. The proposed MDFTN consists of multiple encoders and decoders along with a deep feature transformation module (DFTM). During forward propagation in network training, each encoder extracts diverse features from its respective data source in parallel and the DFTM compresses these features into a shared feature space. Subsequently, each decoder performs an inverse operation for multisource loss estimation. Through collaborative training, the proposed MDFTN leverages the complementary advantages of multisource data distribution to enhance its adaptability and generalization. Numerous experiments were conducted on two public datasets and one local dataset, which demonstrated that the proposed network model can simultaneously process multisource data while effectively suppressing noise and preserving fine structures. The source code is available at https://github.com/123456789ey/MDFTN .
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Background & aims: Macronutrients are the main part of the human diet and can affect multiple health outcomes. Nevertheless, associations between dietary macronutrient quality and asthenozoospermia risk have not been reported to date. Thus, this study aimed to be the first to explore the associations between macronutrient quality and asthenozoospermia risk using the novel multidimensional macronutrient quality index (MQI). Methods: A case-control study was conducted at infertility clinics of Shengjing Hospital of China Medical University during June and December 2020, including 552 asthenozoospermia cases and 585 normozoospermia controls. Data on diet were collected using a validated food frequency questionnaire. MQI was estimated according to the carbohydrate quality index (CQI), fat quality index (FQI), and protein quality index (PQI). Binary logistic regression models were performed to calculate the odds ratio (OR) with a 95% confidence interval (CI). Subgroup and interaction analyses were performed based on age, body mass index, physical activity, smoking, drinking, and education level. Dose-response relationships were evaluated by restricted cubic splines. Sensitivity analyses were performed in two ways. First, participants with a dietary change were excluded to lower potential reverse causation. Then, we used the healthy plate protein source quality index instead of PQI to redefine MQI. Results: No statistically significant association was observed between dietary MQI and asthenozoospermia risk (OR = 1.24, 95% CI: 0.88-1.73). The sub-indices of MQI, CQI, FQI, and PQI, failed to be identified as having a statistically significant association with asthenozoospermia risk (OR = 1.35, 95% CI: 0.92-1.97 for CQI; OR = 1.13, 95% CI: 0.84-1.53 for FQI; OR = 1.28, 95% CI: 0.92-1.78 for PQI). However, CQI showed a positive association with the risk of asthenozoospermia among non-drinkers (Ptrend < 0.05) and highly educated participants (OR = 1.82, 95% CI: 1.13-2.94; Ptrend < 0.05). Additionally, there was a multiplicative interaction between CQI and education level for asthenozoospermia risk (P < 0.05). Conclusions: Our findings demonstrated no association of MQI and its sub-indices with asthenozoospermia risk except for CQI. Although our findings are mostly non-significant, they contribute novel knowledge to this research field and lay the foundation for future studies.
Subject(s)
Asthenozoospermia , Diet , Nutrients , Humans , Male , Case-Control Studies , Adult , China/epidemiology , Nutrients/analysis , Risk Factors , Body Mass IndexABSTRACT
The main aim of this study was to utilize remote sensing data to establish regression models through machine learning to predict locust density in the upcoming year. First, a dataset for monitoring grassland locust density was constructed based on meteorological data and multi-source remote sensing data in the study area. Subsequently, an SVR (support vector regression) model, BP neural network regression model, random forest regression model, BP neural network regression model with the PCA (principal component analysis), and deep belief network regression model were built on the dataset. The experimental results show that the random forest regression model had the best prediction performance among the five models. Specifically, the model achieved a coefficient of determination (R2) of 0.9685 and a root mean square error (RMSE) of 1.0144 on the test set, which were the optimal values achieved among all the models tested. Finally, the locust density in the study area for 2023 was predicted and, by comparing the predicted results with actual measured data, it was found that the prediction accuracy was high. This is of great significance for local grassland ecological management, disaster warning, scientific decision-making support, scientific research progress, and sustainable agricultural development.
ABSTRACT
To compare the short-term outcomes and explore the potential economic benefits of laparoscopic-assisted colectomy with extracorporeal anastomosis (LAC/EA) vs. laparoscopic complete colectomy with intracorporeal anastomosis (LCC/IA) for patients with non-metastatic resectable colon cancer. Data of patients who underwent laparoscopic hemicolectomy from January 2017 to March 2023 were collected and analyzed. Propensity score matching (PSM) analyses was carried out to minimize the selection bias. Before PSM, a total of 113 patients met the inclusion criteria (39 in the LCC/IA vs. 74 in the LAC/EA). Clinicopathologic characteristics were comparable except for the median number of removed lymph nodes (P = 0.023). LCC/IA was associated with longer operative time, less intraoperative blood loss, and shorter incision length. The rate of 30-day postoperative complications was similar, but the time to first flatus and soft diet was shorter in the LCC/IA. No deaths were reported in either group within 30 days after surgery. Costs of surgical instruments (25,945.8 ± 1,918.0 vs. 23,551.9 ± 2,665.5 RMB; P < 0.01) were higher for the LCC/IA but overall costs were similar (LCC/IA, 43,220.0 ± 4,954.0 vs. LAC/EA, 41,269.2 ± 6,685.9 RMB; P = 0.112). After PSM, 38 patients in the LCC/IA and 63 patients in the LAC/EA were compared. LCC/IA was superior in terms of intraoperative blood loss, incision length, and postoperative functional recovery. There was an extra charge of 2385.0 RMB regarding surgical instruments in the LCC/IA but the overall cost did not reach statistical significance. LCC/IA is a feasible, safe, and cost-effective surgical treatment for patients with non-metastatic resectable colon cancer.
ABSTRACT
BACKGROUND: During laparoscopic left hemicolectomy procedures, a previously overlooked consistently thick blood vessel within the gastrocolic ligament near the splenic hilum may contribute to post-operative bleeding complications. The purpose of this study was to investigate the identification and management of the previously overlooked blood vessel. METHODS: This is a retrospective descriptive study of patients undergoing laparoscopic left colectomy for splenic fexure cancer conducted at a national gastrointestinal surgery centre in China. Consecutive patients with splenic fexure cancer who underwent laparoscopic left colectomy using our"five-step process"(n = 34) between January 2021 and July 2023 were included. RESULTS: The vessels can be effectively exposed using the aforementioned "five-step process." It was observed that the overlooked vessels consistently present in all patients were identified as the omental branch of the left gastroepiploic artery and vein. CONCLUSION: We have identified the origin of previously overlooked blood vessels and recommended a safe method for their management. This may offer advantages to colorectal surgeons performing laparoscopic left colectomy for splenic flexure cancer.
Subject(s)
Colectomy , Laparoscopy , Humans , Colectomy/methods , Laparoscopy/methods , Retrospective Studies , Male , Female , Middle Aged , Aged , Colonic Neoplasms/surgery , Colon, Transverse/surgery , Colon, Transverse/blood supply , China , Adult , Postoperative Hemorrhage/etiologyABSTRACT
BACKGROUND: Extrachromosomal circular DNAs (eccDNAs) have been reported to play a key role in the occurrence and development of various diseases. However, the characterization and role of eccDNAs in pulmonary arterial hypertension (PAH) remain unclear. METHODS: In the discovery cohort, we first explored eccDNA expression profiles by Circle-sequencing analysis. The candidate eccDNAs were validated by routine polymerase chain reaction (PCR), TOPO-TA cloning and Sanger sequencing. In the validation cohort, 30 patients with PAH and 10 healthy controls were recruited for qPCR amplification to detect the candidate eccDNAs. Datas at the baseline were collected, including clinical background, biochemical variables, echocardiography and hemodynamic factors. Receiver operating characteristic curve was used to investigate the diagnostic effect of the eccDNA. RESULTS: We identified a total of 21,741 eccDNAs in plasma samples of 3 IPAH patients and 3 individuals in good health, and the expression frequency, GC content, length distribution, and genome distribution of the eccDNAs were thoroughly characterized and analyzed. In the validation cohort, 687 eccDNAs were differentially expressed in patients with IPAH compared with healthy controls (screening threshold: |FC|≥2 and P < 0.05). Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the specific eccDNAs in IPAH were significantly enriched in calcium channel activity, the mitogen-activated protein kinase pathway, and the wnt signaling pathway. Verification queue found that the expression of eccDNA-chr2:131208878-131,424,362 in PAH was considerably higher than that in healthy controls and exhibited a high level of accuracy in predicting PAH with a sensitivity of 86.67% and a specificity of 90%. Furthermore, correlation analysis disclosed a significant association between serum eccDNA-chr2:131208878-131,424,362 and mean pulmonary artery pressure (mPAP) (r = 0.396, P = 0.03), 6 min walking distance (6MWD) (r = -0.399, P = 0.029), N-terminal pro-B-type natriuretic peptide (NT-proBNP) (r = 0.685, P < 0.001) and cardiac index (CI) (r = - 0.419, P = 0.021). CONCLUSIONS: This is the first study to identify and characterize eccDNAs in patients with PAH. We revealed that serum eccDNA-chr2:131208878-131,424,362 is significantly overexpressed and can be used in the diagnosis of PAH, indicating its potential as a novel non-invasive biomarker.
Subject(s)
Biomarkers , DNA, Circular , Humans , Male , Female , Middle Aged , Adult , Biomarkers/blood , DNA, Circular/blood , DNA, Circular/genetics , DNA, Circular/analysis , Pulmonary Arterial Hypertension/blood , Pulmonary Arterial Hypertension/genetics , Pulmonary Arterial Hypertension/diagnosis , Cohort Studies , Case-Control StudiesABSTRACT
PURPOSE: Diabetic bladder fibrosis is a common comorbidity. Altered expression of some long non-coding RNAs (LncRNAs) has been associated with bladder fibrosis. LncRNA H19 has been reported to regulate bladder cancer through miR-29b. However, the action mechanism of LncRNA H19 in bladder fibrosis is unclear. METHODS: In vitro, human bladder smooth muscle cells (HBSMCs) were cultured with transforming growth factor-ß1 (TGF-ß1) for 48 h to construct cell model of bladder fibrosis. HBSMCs were then transfected with si-LncRNA H19, si-NC, miR-29b-mimic, mimic-NC, or miR-29b-inhibitor. In vivo, Sprague-Dawley (SD) rats were given a high-sucrose-high-fat (HSHF) diet for 4 weeks and injected with streptozotocin (STZ, 50 mg/kg) to induce bladder fibrosis model in diabetic rats, followed by injection of lentiviral particles knocking down LncRNA H19 expression, empty vector, or miR-29b-inhibitor, respectively. RESULTS: LncRNA H19 was up-regulated in TGF-ß1-induced HBSMC fibrosis and STZ-induced diabetic rat bladder fibrosis, whereas miR-29b was down-regulated. si-LncRNA H19 reduced blood glucose levels and improved histopathological damage of bladder tissue in rats. In addition, si-LncRNA H19 or miR-29b-mimic increased the expression of E-cadherin, but decreased the expression of N-cadherin, vimentin, fibronectin (FN) in bladder tissues, and HBSMCs. si-LncRNA H19 reduced TGF-ß1/p-drosophila mothers against decapentaplegic 3 (Smad3) protein in HBSMCs and in rat bladder tissues, while miR-29b-inhibitor reversed the effect of si-LncRNA H19. CONCLUSION: This study indicated that LncRNA H19 may inhibit bladder fibrosis in diabetic rats by targeting miR-29b via the TGF-ß1/Smad3 signalling pathway.
Subject(s)
Diabetes Mellitus, Experimental , Fibrosis , MicroRNAs , RNA, Long Noncoding , Rats, Sprague-Dawley , Signal Transduction , Transforming Growth Factor beta1 , Animals , RNA, Long Noncoding/metabolism , RNA, Long Noncoding/genetics , MicroRNAs/metabolism , MicroRNAs/genetics , Rats , Transforming Growth Factor beta1/metabolism , Diabetes Mellitus, Experimental/complications , Humans , Cells, Cultured , Urinary Bladder/pathology , Urinary Bladder/metabolism , Male , Urinary Bladder Diseases/metabolism , Urinary Bladder Diseases/etiology , Smad3 Protein/metabolismABSTRACT
TECHNIQUE: We describe improvements to the previously proposed "U-tied anastomosis" with the aim of broadening its indications, especially in left hemicolectomy. After bowel mobilization and vascular ligation, the proximal and distal colon were aligned in a U-shape using a ligature. An anastomosis was constructed using a linear stapler through the common enterotomies. Following resection of the bowel using laparoscopic coagulation shears, the common opening was closed using 3-0 barbed sutures. RESULTS: Eight consecutive patients underwent colectomy using the U-tied semi-manual technique between May and July 2023. In all cases, the U-tied procedures were completed using one cartridge and two sutures. No complications or mortality were observed after one month of follow-up. CONCLUSIONS: The U-tied semi-manual anastomosis is a straightforward and effective method for intracorporeal anastomosis. The simplified reconstruction technique of U-tied series, together with the minimization of technique variability, results in consistent outcomes when performed by surgeons with different levels of experience. The streamlined process enhances the homogeneity of the intracorporeal anastomosis while reducing cartridge use.
Subject(s)
Laparoscopy , Surgeons , Humans , Colectomy , Anastomosis, Surgical , SuturesABSTRACT
Diketopiperazine alkaloids have proven the most abundant heterocyclic alkaloids up to now, which usually process diverse scaffolds and rich biological activities. In our search for bioactive diketopiperazine alkaloids from marine-derived fungi, two novel diketopiperazine alkaloids, penipiperazine A (1) and its biogenetically related new metabolite (2), together with a known analogue neofipiperzine C (3), were obtained from the strain Penicillium brasilianum. Their planar structures and absolute configurations were elucidated by extensive spectroscopic analyses, 13C NMR calculation, Marfey's, ECD, and ORD methods. Compound 1 featured a unique 6/5/6/6/5 indole-pyrazino-pyrazino-pyrrolo system, and its plausible biogenetic pathway was also proposed. Additionally, compounds 1-3 have been tested for their inflammatory activities. 1 and 2 significantly inhibited the release of NO and the expression of related pro-inflammatory cytokines on LPS-stimulated RAW264.7 cells, suggesting they could be attracting candidate for further development as anti-inflammatory agent. KEY POINTS: ⢠A novel diketopiperazine alkaloid featuring a unique 6/5/6/6/5 indole-pyrazino-pyrazino-pyrrolo system was isolated from the marine fungus Penicillium brasilianum. ⢠The structure of 1 was elucidated by detailed analysis of 2D NMR data, 13C NMR calculation, Marfey's, ECD, and ORD methods. ⢠Compounds 1 and 2 significantly inhibited the release of NO and the expression of related pro-inflammatory cytokines on LPS-stimulated RAW264.7 cells.
Subject(s)
Alkaloids , Penicillium , Diketopiperazines/pharmacology , Lipopolysaccharides , Fungi , Alkaloids/chemistry , Indoles , Anti-Inflammatory Agents/pharmacology , Cytokines , Molecular Structure , Indole Alkaloids/pharmacology , Indole Alkaloids/chemistryABSTRACT
We have accomplished the first and asymmetric total synthesis of principinol B, a grayanoid possessing an oxabicyclo[3.2.1] architecture. A functionalized 5/7/6/5 tetracyclic intermediate was assembled in a convergent manner by a diastereoselective intermolecular aldol reaction and subsequent carbonyl-olefin metathesis of two enantiomerically enriched fragments. The oxabicyclo[3.2.1] architecture containing a 6,10-ether bridge was constructed by the Williamson ether synthesis.
ABSTRACT
Increasing attention is being given to machine learning methods designed to aid clinicians in treatment selection. Therefore, this has aroused a heightened focus on the auto-detect system of epilepsy utilizing electroencephalogram(EEG) data. However, in order for the recognition model to accurately capture a wide range of features related to channel, frequency, and temporal information, it is necessary to have EEG data that is correctly represented. To tackle this challenge, we propose a Residual-based Inception with Hybrid-Attention Network(RIHANet) to achieve automatic seizure detection. Initially, by employing Empirical Mode Decomposition and Short-time Fourier Transform(EMD-STFT) for data processing, it can improve the quality of time-frequency representation of EEG. Additionally, by applying a novel Residual-based Inception to the network architecture, the detection model can learn local and global multiscale spatial-temporal features. Furthermore, the Hybrid Attention model designed is used to obtain relationships between EEG signals from multiple perspectives, including channels, sub-spaces, and global. Using four public datasets, the suggested approach outperforms the results in the most recent scholarly publications.
Subject(s)
Epilepsy , Signal Processing, Computer-Assisted , Humans , Seizures/diagnosis , Epilepsy/diagnosis , Machine Learning , Electroencephalography/methods , AlgorithmsABSTRACT
Rotational Bose-Einstein condensates can exhibit quantized vortices as topological excitations. In this study, the ground and excited states of the rotational Bose-Einstein condensates are systematically studied by calculating the stationary points of the Gross-Pitaevskii energy functional. Various excited states and their connections at different rotational frequencies are revealed in solution landscapes constructed with the constrained high-index saddle dynamics method. Four excitation mechanisms are identified: vortex addition, rearrangement, merging, and splitting. We demonstrate changes in the ground state with increasing rotational frequencies and decipher the evolution of the stability of ground states.
ABSTRACT
The current criteria for utilizing MDM2 Fluorescence In Situ Hybridization (FISH) in adipose-derived tumors were first introduced in 2015 and have been widely adopted. However, these criteria may fail to identify some atypical lipomatous tumors / well-differentiated liposarcoma (ALT/WDL) with mature adipocytic morphology in clinical practice, possibly due to the fact that the existing criteria are primarily based on biopsy cases. Hence, a criterion based on resection cases is needed. In this study, we included 87 adipose tissue tumors with mature adipocytic morphology which were first resected, as well as 9 consultation cases and 25 recurrent resection cases. The final diagnosis was based on MDM2 amplification status. Among the 87 first-time resection cohort, MDM2 FISH amplification was observed in only 2 (5%) of the 39 superficial cases. Marginal infiltration was significantly different in both the MDM2 FISH negative and positive groups (p < 0.05). Of the 37 intramuscular tumors, 17 (46%) showed MDM2 FISH amplification. The MDM2 amplification positive group had a larger tumor size than MDM2 amplification negative group (p = 0.042). Tumors of larger size (≥11 cm) were highly correlated with MDM2 amplification (p = 0.003), but still, 35.3% of the MDM2 amplification-positive cases had tumor sizes less than 11 cm. Eight (66.7%) out of twelve retroperitoneal/ pelvic cases were MDM2 FISH positive. Among the 25 recurrent cases, twenty (80%) of them had MDM2 FISH amplification. In conclusion, we recommend MDM2 FISH for: 1. superficial cases with marginal infiltration based on adequate margin sampling; 2. all intramuscular tumors, retroperitoneal/pelvic tumors and recurrent tumors, both in resection cases and biopsy cases.
Subject(s)
Lipoma , Liposarcoma , Retroperitoneal Neoplasms , Humans , Liposarcoma/diagnosis , Liposarcoma/genetics , Liposarcoma/pathology , In Situ Hybridization, Fluorescence , Gene Amplification , Proto-Oncogene Proteins c-mdm2/genetics , Proto-Oncogene Proteins c-mdm2/metabolism , Neoplasm Recurrence, Local/diagnosis , Lipoma/diagnosis , Biomarkers, TumorABSTRACT
STUDY QUESTION: Is dietary non-enzymatic antioxidant capacity related to semen quality? SUMMARY ANSWER: The only statistically significant association of semen quality parameters with dietary total antioxidant capacity (DTAC) detected was an inverse association between DTAC and ejaculate volume. WHAT IS KNOWN ALREADY: Growing interest exists regarding the role of diet in influencing semen quality. While DTAC is linked to favorable health outcomes, its association with semen quality, especially among men attending infertility clinics, remains understudied. STUDY DESIGN SIZE DURATION: This cross-sectional study was carried out between June and December of 2020. In total, 1715 participants were included in the final analysis. PARTICIPANTS/MATERIALS SETTING METHODS: Men who attended an infertility clinic in China were enrolled. Experienced clinical technicians performed the semen analysis. The DTAC indices included the ferric-reducing ability of plasma, oxygen radical absorbance capacity, total reactive antioxidant potential, and Trolox equivalent antioxidant capacity. The quantile regression model was used for multivariate analysis. MAIN RESULTS AND THE ROLE OF CHANCE: After adjustment for a variety of confounding variables, a significant inverse association was identified between DTAC and ejaculate volume (ßcontinuous FRAP = -0.015, 95% CI = -0.023, -0.006, ßT3 vs T1 = -0.193, 95% CI = -0.379, -0.006, Ptrend = 0.007; ßcontinuous TRAP = -0.019, 95% CI = -0.041, 0.002, ßT3 vs T1 = -0.291, 95% CI = -0.469, -0.112, Ptrend = 0.002). The majority of DTAC indices have no statistically significant association with semen quality parameters. LIMITATIONS REASONS FOR CAUTION: We cannot infer causality because of the nature of the cross-sectional study design. The robustness of the conclusion may be compromised by the exactness of non-enzymatic antioxidant capacity estimation. WIDER IMPLICATIONS OF THE FINDINGS: Our findings demonstrated no association between DTAC indices and semen quality parameters among men attending an infertility clinic, except for ejaculate volume. Even though our findings are mostly non-significant, they contribute novel knowledge to the field of study while also laying the groundwork for future well-designed studies. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the JieBangGuaShuai Project of Liaoning Province [grant number 2021JH1/10400050], the Clinical Research Cultivation Project of Shengjing Hospital [grant number M1590], and the Outstanding Scientific Fund of Shengjing Hospital [grant number M1150]. The sponsors had no role in study design, or in the collection, analysis, and interpretation of data, or in the writing of the report, or in the decision to submit the article for publication. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.
ABSTRACT
Intrahepatic cholangiocarcinoma (iCCA) is classified by the 5th WHO classification of tumours of the digestive system as large duct type (LDT) and small duct type (SDT), based on the anatomical location, morphological appearances, immunophenotype, and gene events. We evaluated the subtyping system using real-world data and established a supplementary method using immunohistochemical (IHC) detection. We retrospectively investigated 190 cases of surgically resected iCCA and classified them according to histological evaluations and gene detection. The prognostic value of the IHC markers were evaluated according to the relapse-free survival (RFS) and overall survival (OS). Basic histological classification was insufficient, with 61 cases classified as uncertain. This method showed no prognostic value for RFS or OS. The four-marker IHC detection, including EMA, S100P, N-cadherin, and CRP, which classified 68 cases as LDT, 108 cases as SDT, and 14 cases as uncertain, was highly efficient in subtyping and prognosis. The seven-marker method, including CD56, MUC5AC and MUC6, was consistent with the four-marker method. FGFR2 gene fusion was exclusively detected in 20 cases of SDT iCCA, according to the four- and seven-marker IHC detection. This novel method of iCCA classification exhibited diagnostic, prognostic and therapeutic value in clinical practice.
Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Humans , Prognosis , Retrospective Studies , Neoplasm Recurrence, Local , Cholangiocarcinoma/diagnosis , Cholangiocarcinoma/genetics , Bile Duct Neoplasms/diagnosis , Bile Duct Neoplasms/genetics , Bile Ducts, Intrahepatic/pathologyABSTRACT
Eight previously undescribed indole-diterpenoids named penerpenes O-V (1-8), together with seven known analogues (9-14), were isolated from the marine soft coral-derived fungus Aspergillus sp. ZF-104. Their structures including the absolute configurations of these compounds were assigned on the basis of spectroscopic data and ECD analysis along with quantum ECD and NMR calculations. Compounds 4 and 5 bear rare indolin-2-one units in their structures and 6 bears a reconstructed novel skeleton in which the indole ring and the terpenoid substructure are cleaved before they are reconnected through the nitrogen atom. Compounds 1, 2, 7, and 10 showed protein tyrosine phosphatase 1B (PTP1B) inhibitory activities comparable to that of the positive control NaVO3.